Document:

<PAGE>
                                                                    Exhibit 10.6

                                                                [EXECUTION COPY]

                                 AMENDMENT NO. 1
                                       TO
                                CREDIT AGREEMENT

         This AMENDMENT NO. 1, dated as of June 25, 2002 (this "AMENDMENT"), is
made by and among SIERRA PACIFIC POWER COMPANY, a Nevada corporation (the
"BORROWER"), the banks listed on the signature pages of this Amendment as
"Lenders" (such banks, together with their respective permitted assignees from
time to time, being referred to herein, collectively, as the "LENDERS"), and
UNION BANK OF CALIFORNIA, N.A. ("UNION BANK"), as administrative agent for the
Lenders (the "ADMINISTRATIVE AGENT").

                             PRELIMINARY STATEMENTS:

         (1)      The Borrower, the Lenders, the Administrative Agent, Union
Bank, as Sole Bookrunner, Wells Fargo Bank, N.A., as Syndication Agent, and Bank
One, NA, BNP Paribas and Mellon Bank, N.A., as Co-Documentation Agents,
previously entered into that certain Credit Agreement, dated as of November 30,
2001 (the "EXISTING AGREEMENT", as further amended by this Amendment, the
"AMENDED AGREEMENT", and as the Amended Agreement may hereafter be amended,
supplemented or otherwise modified from time to time, the "CREDIT AGREEMENT").
Capitalized terms used and not otherwise defined herein shall have the meanings
assigned thereto in the Existing Agreement.

         (2)      As contemplated at the time of executing the Existing
Agreement, the Borrower plans to enter into a receivables purchase facility (the
"RECEIVABLES PURCHASE FACILITY") with certain financial institutions (the
"PURCHASERS"). Under the Receivables Purchase Facility, (a) the Borrower will
sell accounts receivable arising from the provision of electricity or natural
gas to a newly created, wholly-owned bankruptcy remote special purpose
subsidiary of the Borrower (the "SPV") and (b) either (i) the SPV (or a newly
created, wholly-owned bankruptcy remote special purpose subsidiary of Sierra
Pacific Resources (the "PARENT SPV") to which the SPV may first sell such
accounts receivable) will sell undivided percentage ownership interests in such
accounts receivable (the "PURCHASER INTERESTS") to the Purchasers, or (ii) the
Purchasers will make advances ("ADVANCES") to the SPV or the Parent SPV in
respect of and secured by such accounts receivable.
<PAGE>
                                                                               2

         (3)      Although it was the parties' intention that the Existing
Agreement permit the establishment of the Receivables Purchase Facility to
enhance the Borrower's liquidity and overall financial position, during the
course of preparing the documentation for the Receivables Purchase Facility, it
has become apparent that certain provisions of the Existing Agreement restrict
the capacity of the Receivables Purchase Facility to achieve those objectives.

         (4)      Accordingly, the Borrower now wishes to amend the Existing
Agreement to clarify that the Borrower may enter into the transactions
contemplated by the Receivables Purchase Facility. The Borrower also wishes to
amend Section 6.02 and other provisions of the Existing Agreement in certain
particulars. The Required Lenders and the Administrative Agent have agreed to
such amendments, on the terms and conditions set forth herein.

         NOW, THEREFORE, for good and valuable consideration, the receipt and
sufficiency of which is hereby acknowledged, the parties hereto hereby agree as
follows:

         SECTION 1. AMENDMENTS TO EXISTING AGREEMENT. The Existing Agreement is,
effective as of the date hereof and subject to the satisfaction of the
conditions precedent set forth in Section 2 hereof, hereby amended as follows:

         (a)      NEW DEFINITIONS. The following new definitions are hereby
added to Section 1.01 in the appropriate alphabetical order:

                  "ADVANCES" has the meaning assigned to such term in the
         definition of "Receivables Purchase Facility" contained in this Section
         1.01.

                  "DISPOSE" has the meaning assigned to such term in Section
         6.04; and the terms "DISPOSITION" and "DISPOSED" shall have correlative
         meanings.

                  "MINIMUM ADVANCE PERCENTAGE" means, in respect of any
         Receivables Purchase Facility, a percentage equal to the greater of (i)
         80% less the reserves (expressed as a percentage) established under
         such Receivables Purchase Facility in respect of dilutive factors with
         respect to the accounts receivable Disposed of to the Purchasers
         thereunder or securing Advances thereunder, as the case may be, or (ii)
         70%.

                  "PARENT SPV" has the meaning assigned to such term in the
         definition of "Receivables Purchase Facility" contained in this Section
         1.01.

                  "PURCHASE CONTRACT L/C" has the meaning assigned to such term
         in Section 6.02(i).
<PAGE>
                                                                               3

                  "PURCHASER INTERESTS" has the meaning assigned to such term in
         the definition of "Receivables Purchase Facility" contained in this
         Section 1.01.

                  "PURCHASERS" has the meaning assigned to such term in the
         definition of "Receivables Purchase Facility" contained in this Section
         1.01.

                  "RECEIVABLES PURCHASE FACILITY" means an accounts receivable
         purchase facility pursuant to which (a) the Borrower will sell accounts
         receivable arising from the provision of electricity or natural gas to
         a newly created, wholly-owned bankruptcy remote special purpose
         subsidiary of the Borrower (the "SPV") and (b) either (i) the SPV (or a
         newly created, wholly-owned bankruptcy remote special purpose
         subsidiary of Sierra Pacific Resources (the "PARENT SPV") to which the
         SPV may first sell such accounts receivable) will sell undivided
         percentage ownership interests in such accounts receivable (the
         "PURCHASER INTERESTS") to the various financial institutions party to
         such facility (the "PURCHASERS"), or (ii) the Purchasers will make
         advances ("ADVANCES") to the SPV or the Parent SPV in respect of and
         secured by such accounts receivable.

                  "RELATED SECURITY" means, with respect to any accounts
         receivable of the Borrower, the SPV or the Parent SPV (as applicable),
         (i) all Liens and property subject thereto from time to time, if any,
         purporting to secure payment of such accounts receivable, whether
         pursuant to the contract related to such accounts receivable or
         otherwise, (ii) all guaranties, letters of credit, insurance and other
         agreements or arrangements of whatever character from time to time
         supporting or securing payment of such accounts receivable whether
         pursuant to the contract related to such accounts receivable or
         otherwise, (iii) all service contracts and other contracts and
         agreements associated with such accounts receivable, (iv) all books and
         records related to such accounts receivable, and (v) all proceeds of
         any of the foregoing.

                  "SPV" has the meaning assigned to such term in the definition
         of "Receivables Purchase Facility" contained in this Section 1.01.

         (b)      REPORTING REQUIREMENTS. Section 5.01 is hereby amended by
adding the following new subsections (k) and (l) at the end thereof:
<PAGE>
                                                                               4

                  "(k)     CASH RECEIPTS AND DISBURSEMENTS. The Borrower shall
         deliver to the Administrative Agent, with a copy for each Lender, on
         the first Wednesday of every two-calendar-week period, a statement of
         projected weekly cash receipts and cash disbursements for at least the
         immediately succeeding 12-calendar-week period, together with a
         comparison of the projected cash receipts and disbursements to actual
         cash receipts and disbursements for the immediately preceding
         two-calendar-week period, in each case in substantially the form set
         forth as Exhibit E, duly completed and signed by a Responsible Officer
         of the Borrower.

                  (l)      MONTHLY FINANCIAL REPORTS. As soon as practicable,
         and in any event within three Business Days, after the Borrower issues
         its monthly management-prepared financial statements, the Borrower
         shall deliver such financial statements to the Administrative Agent,
         with a copy for each Lender."

         (c)      LIENS.  Section 6.02 is hereby amended by:

                  (i)      deleting the word "and" after the semicolon at the
         end of subsection (g) thereof;

                  (ii) deleting clause (iv) contained in the proviso to
         subsection (h) thereof in its entirety and substituting therefor the
         following new clause (iv):

                  "(iv) the aggregate amount secured by all Liens described in
                  this Section 6.02(h) shall not at any time exceed (A)
                  $50,000,000 minus (B) the aggregate amount of cash, cash
                  equivalents, marketable securities, instruments and other
                  investment property held in deposit accounts, investment
                  accounts or otherwise with any financial and/or depository
                  institutions and subject to a Lien permitted under subsection
                  (i) below;"

                  (iii)    deleting the period at the end of subsection (h)
         thereof;

                  (iv)     adding the following new subsection (i) immediately
         after subsection (h) thereof:

                           "(i) Liens, including pledges, rights of offset and
                  bankers' liens, on deposit accounts, instruments, investment
                  accounts and investment property (including cash, cash
                  equivalents and marketable securities) from time to time
                  maintained with or held by any financial and/or

<PAGE>
                                                                               5

                  depository institutions, in each case solely to secure (1) any
                  and all obligations of the Borrower in respect of letters of
                  credit issued from time to time by any such financial and/or
                  depository institutions (or their Affiliates) for the account
                  of the Borrower or any of its Subsidiaries for purposes of
                  supporting the Borrower's or such Subsidiary's obligations now
                  or hereafter owing to gas or other energy suppliers (such
                  letters of credit, collectively, the "PURCHASE CONTRACT
                  L/C'S"), or (2) any and all obligations now or hereafter
                  existing of the Borrower or any of its Subsidiaries in
                  connection with any deposit account, investment account or
                  cash management service (including ACH, Fedwire, CHIPS,
                  concentration and zero balance accounts, and controlled
                  disbursement, lockbox or restricted accounts) now or hereafter
                  provided by any financial and/or depository institutions to or
                  for the benefit of the Borrower, any of its Subsidiaries or
                  any special purpose entity directly or indirectly providing
                  loans to or making receivables purchases from the Borrower or
                  any of its Subsidiaries; PROVIDED, HOWEVER, that the aggregate
                  amount of cash, cash equivalents, marketable securities,
                  instruments and other investment property held in deposit
                  accounts, investment accounts or otherwise with any financial
                  and/or depository institutions and subject to a Lien permitted
                  under this Section 6.02(i) shall not at any time exceed (A)
                  $50,000,000 minus (B) the aggregate amount secured by Liens
                  described in subsection (h) above; and"

         and

                  (v)      adding the following new subsection (j) immediately
         after the new subsection (i) thereof:

                           "(j) Liens in the SPV's accounts receivable and
                  Related Security securing the obligations of the SPV under a
                  Receivables Purchase Facility permitted under Section 6.04(c)
                  (including, without limitation, the SPV's obligation to repay
                  Advances made thereunder)."

         (d)      DISPOSITIONS OF PROPERTIES. Section 6.04 is hereby amended in
its entirety to read as follows:

                  "SECTION 6.04  Dispositions of Properties.

                  The Borrower shall not, and shall not permit any of its
         Subsidiaries to, sell, convey, assign, lease, sale-leaseback, transfer,
         abandon or

<PAGE>
                                                                               6

         otherwise dispose of, voluntarily or involuntarily (collectively,
         "DISPOSE"), any of its Properties, or agree, become or remain liable
         contingently or otherwise to do any of the foregoing, except that, so
         long as no Default or Event of Default shall have occurred and be
         continuing or shall exist at such time or after giving effect to such
         transaction, the Borrower and its Subsidiaries may Dispose of Property
         (a) in transactions in the ordinary course of business consistent with
         past practice, (b) that is obsolete, (c) comprising accounts receivable
         and Related Security transferred from time to time on a revolving basis
         to the SPV, the Parent SPV, a commercial paper conduit or other
         purchaser pursuant to a Receivables Purchase Facility; PROVIDED that
         (i) the outstanding amount of capital associated with the Purchaser
         Interests that are Disposed of, or the outstanding amount of Advances
         made in respect of such Disposed accounts receivable, as the case may
         be, pursuant to all Receivables Purchase Facilities does not exceed
         $125,000,000 in the aggregate as of any date of determination, and (ii)
         the aggregate net cash proceeds received by the Borrower for all
         Dispositions of accounts receivable and Related Security made pursuant
         to, or in connection with, Receivables Purchase Facilities are not less
         than the Minimum Advance Percentage of the aggregate amount of accounts
         receivable Disposed of in all such Dispositions; PROVIDED, HOWEVER,
         that, notwithstanding the foregoing, upon the occurrence and during the
         continuance of a Default or an Event of Default, the Borrower and its
         Subsidiaries may continue to Dispose of accounts receivable and Related
         Security pursuant to this clause (c) if (and only if) (A) the
         conditions set forth in clauses (i) and (ii) above are satisfied at the
         time of each such Disposition and (B) the cash proceeds received by the
         Borrower for each such Disposition are applied immediately as a
         prepayment of the Loans pursuant to Section 2.08(b); PROVIDED, FURTHER,
         that each Disposition made by the Borrower in reliance on this clause
         (c) shall constitute a representation and warranty of the Borrower,
         made at the time of such Disposition, that the conditions set forth in
         clauses (i) and (ii) above are satisfied at such time, and (d) in
         transactions other than as provided in Section 6.04(a), (b) and (c);
         PROVIDED that the aggregate book value of all Property Disposed of
         pursuant to this Section 6.04(d) from and after the date hereof shall
         not exceed $50,000,000."

         (e)      DIVIDENDS AND STOCK REPURCHASES. Section 6.06 is hereby
amended in its entirety to read as follows:

                  "SECTION 6.06  DIVIDENDS AND STOCK REPURCHASES.

                  The Borrower shall not declare or pay, directly or indirectly,
         any dividend, payment or other distribution of assets, properties,
         cash, rights, obligations or securities on account of any share of any
         class of capital stock of the Borrower (except for dividends in the
         form of capital stock), or make any distribution of

<PAGE>
                                                                               7

         assets to any of its shareholders, in each case if a Default or Event
         of Default shall have occurred and be continuing or shall exist at such
         time or after giving effect to such transaction. The Borrower shall not
         purchase, redeem, retire, or otherwise acquire for value any shares of
         any class of capital stock of the Borrower or any warrants, rights, or
         options to acquire any such shares, now or hereafter outstanding."

         (f)      EQUAL AND RATABLE LIEN. Section 6.09(a) is hereby amended by
deleting the period at the end of the first sentence thereof and inserting in
lieu thereof the following:

         "; PROVIDED, HOWEVER, that, subject to Section 2.15(d), no issuer of a
         Purchase Contract L/C shall be required to share with the Lenders any
         collateral granted to such issuer pursuant to Section 6.02(i)(1) if (i)
         such issuer received from the Borrower at the time of the issuance of
         such Purchase Contract L/C a written representation and warranty
         confirming the Borrower's compliance with the provisions of Section
         6.02(i) in connection therewith and (ii) such issuer had no actual
         knowledge at the time of such issuance that the Lien granted by the
         Borrower or any of its Subsidiaries (as the case may be) in such
         collateral constituted a violation of Section 6.02."

         (g)      RESTRICTIVE AGREEMENTS. Section 6.10(a) is hereby amended by
deleting the phrase "the Borrower or any of its Subsidiaries to create" in its
entirety and substituting therefor the new phrase "the Borrower or any of its
Subsidiaries (other than the SPV and/or the Parent SPV in connection with a
Receivables Purchase Facility) to create".

         (h)      PREPAYMENTS AND REDEMPTION OF INDEBTEDNESS. Article VI is
hereby amended by adding the following new Section 6.11 at the end thereof:

                  "SECTION 6.11 PREPAYMENTS AND REDEMPTION OF INDEBTEDNESS.

                  The Borrower shall not purchase, redeem, retire or otherwise
         acquire for value, or set apart any money for a sinking, defeasance or
         other analogous fund for the purchase, redemption, retirement or other
         acquisition of, or make any voluntary payment or prepayment of the
         principal of or interest on, or any other amount owing in respect of,
         any of its Indebtedness (other than Indebtedness hereunder and under
         the other Loan Documents), except that (i) the Borrower may make
         payments on the regularly-scheduled payment dates with respect to the
         principal of and interest on its Indebtedness and (ii) the Borrower may
         reimburse the issuer of any letter of credit or similar instrument
         issued for the

<PAGE>

                                                                               8

         account of the Borrower (in each case to the extent such letter of
         credit or similar instrument is permitted to be issued for the account
         of the Borrower pursuant to the terms of this Agreement) for any
         drawings made thereunder, together with any interest and fees related
         thereto, at the times required under any reimbursement agreement or
         similar agreement to which the Borrower is a party, and (iii) for the
         avoidance of doubt, this Section 6.11 shall not prohibit any payments
         or prepayments of amounts payable (including, without limitation,
         deferred amounts payable) (other than for borrowed money) to the
         Borrower's gas and power suppliers arising in the ordinary course of
         business."

         (i)      NEW EXHIBIT. Exhibit E attached hereto is hereby deemed to
constitute Exhibit E to the Credit Agreement.

         SECTION 2. CONDITIONS OF EFFECTIVENESS. This Amendment shall become
effective (a) with respect Sections 1(c)(v), 1(d) and 1(g) hereof, as of July 8,
2002, and (b) with respect to all other provisions contained in Section 1
hereof, as of the date first above written, when, and only when, the
Administrative Agent shall have received: (i) counterparts of this Amendment
executed by the Borrower, the Administrative Agent and the Required Lenders,
(ii) for the account of each Lender that delivers an executed counterpart of
this Amendment on or before June 25, 2002, a nonrefundable amendment fee of
0.30% of such Lender's Commitment, in immediately available funds, and (iii) all
of the following documents, each document being dated the date of receipt
thereof by the Administrative Agent (which date shall be the same for all such
documents), in form and substance satisfactory to the Administrative Agent:

                  (A)      A certificate of the Secretary or an Assistant
         Secretary of the Borrower certifying the names, true signatures and
         incumbency of the officers of the Borrower authorized to sign this
         Amendment and any other documents to be delivered hereunder.

                  (B)      A certificate of a Responsible Officer of the
         Borrower (the statements in which shall be true) stating that (1)
         except as disclosed by Sierra Pacific Resources in its press release
         issued on June 11, 2002, the representations and warranties set forth
         in Article III of the Existing Agreement are true and correct on and as
         of the date hereof, both before and after giving effect to this
         Amendment, as though made on and as of such date, and (2) after giving
         effect to this Amendment, no event has occurred and is continuing that
         constitutes a Default or an Event of Default, and no Default or Event
         of Default would result from the execution, delivery or performance of
         this Amendment or the transactions contemplated hereby.

         SECTION 3. REPRESENTATIONS AND WARRANTIES OF THE BORROWER. The Borrower
represents and warrants as follows:

<PAGE>
                                                                               9

         (a)      The execution and delivery by the Borrower of this Amendment,
and the performance by the Borrower of this Amendment and the Amended Agreement,
(i) are within the Borrower's corporate powers, (ii) have been duly authorized
by all necessary corporate action, and (iii) do not and will not (A) require any
consent or approval of the shareholder of the Borrower (other than any such
consent or approval that has been duly obtained and is in full force and
effect), (B) violate any provision of the articles of incorporation or by-laws
of the Borrower or of law, (C) violate any legal restriction binding on or
affecting the Borrower, (D) result in a breach of, or constitute a default
under, any indenture or loan or credit agreement or any other agreement, lease
or instrument to which the Borrower is a party or by which it or its properties
may be bound or affected, or (E) result in or require the creation of any Lien
(other than pursuant to the Loan Documents) upon or with respect to any of its
properties. This Amendment has been duly executed and delivered by the Borrower.

         (b)      No Governmental Action is required for (i) the due execution
and delivery by the Borrower of this Amendment or (ii) the performance by the
Borrower of this Amendment and the Amended Agreement, other than any such
Governmental Actions that have been duly obtained or made and are in full force
and effect on the date hereof.

         (c)      Each of this Amendment and the Amended Agreement is the legal,
valid and binding obligation of the Borrower enforceable against the Borrower in
accordance with its respective terms, except as such enforceability may be
limited by bankruptcy, insolvency, reorganization, moratorium or other laws
affecting the enforcement of creditors' rights generally and by general
equitable principles (regardless of whether such enforceability is considered in
a proceeding in equity or at law).

         (d)      Except as disclosed by the Borrower in its reports filed with
the Securities and Exchange Commission prior to the date hereof, there is no
pending or, to the knowledge of the Borrower, threatened action, suit,
investigation, litigation or proceeding affecting the Borrower or any of its
properties before any court, governmental agency or arbitrator, that would
reasonably be expected to materially adversely affect the legality, validity, or
enforceability of, or the ability of the Borrower to perform its obligations
under, this Amendment or the Amended Agreement.

         SECTION 4. REFERENCE TO AND EFFECT ON THE EXISTING AGREEMENT. (a) Upon
the effectiveness of this Amendment: (i) each reference in the Existing
Agreement to "this Agreement", "hereunder", "hereof" or words of like import
referring to the Existing Agreement shall mean and be a reference to the Amended
Agreement; and (ii) each reference in any other Loan Document to "the Credit
Agreement", "thereunder", "thereof" or words of like import referring to the
Existing Agreement shall mean and be a reference to the Amended Agreement.
<PAGE>
                                                                              10

         (b)      Except as specifically amended above, the Existing Agreement
shall continue to be in full force and effect and is hereby in all respects
ratified and confirmed.

         (c)      The execution, delivery and effectiveness of this Amendment
shall not, except as expressly provided herein, operate as a waiver of any
right, power or remedy of the Lenders or the Administrative Agent under the
Existing Agreement or any other Loan Document, nor constitute a waiver of any
provision of the Existing Agreement or any other Loan Document.

         SECTION 5. COSTS AND EXPENSES. The Borrower agrees to pay on demand (i)
all reasonable costs and expenses of the Administrative Agent in connection with
the preparation, negotiation, syndication, execution, delivery, administration
and performance of this Amendment, the Amended Agreement, the other Loan
Documents and the other instruments and documents to be delivered hereunder,
including, without limitation, the reasonable fees and out-of-pocket expenses of
(A) counsel to the Administrative Agent with respect thereto and with respect to
advising the Administrative Agent as to its rights and responsibilities
hereunder and thereunder, and (B) any other consultants or experts that the
Administrative Agent reasonably deems necessary or advisable in connection with
the foregoing, and (ii) all costs and expenses of the Administrative Agent and
each Lender (including, without limitation, reasonable fees and expenses of (A)
counsel to the Administrative Agent and counsel for each Lender and (B) any
other consultants or experts deemed necessary or advisable by the Administrative
Agent) in connection with the enforcement or preservation of rights (whether
through negotiations, legal proceedings or otherwise) under this Amendment, the
Amended Agreement or any other Loan Document.

         SECTION 6. EXECUTION IN COUNTERPARTS. This Amendment may be executed in
any number of counterparts and by different parties hereto in separate
counterparts, each of which when so executed and delivered shall be deemed to be
an original and all of which taken together shall constitute but one and the
same instrument. In furtherance of the foregoing, it is understood and agreed
that signatures hereto submitted by facsimile transmission shall be deemed to
be, and shall constitute, original signatures.

         SECTION 7. GOVERNING LAW. This Amendment shall be governed by, and
construed in accordance with, the laws of the State of the New York.

                  [REMAINDER OF PAGE INTENTIONALLY LEFT BLANK]
<PAGE>
                                                                             S-1

         IN WITNESS WHEREOF, the parties hereto have caused Amendment to be
executed by their respective officers thereunto duly authorized, as of the date
first above written.

                                        SIERRA PACIFIC POWER COMPANY

                                        By
                                          -----------------------------------
                                          Name:
                                          Title:

                                        UNION BANK OF CALIFORNIA, N.A., as
                                        Administrative Agent

                                        By
                                          -----------------------------------
                                          Name:
                                          Title:

           Signature Page to Amendment No. 1 to SPPC Credit Agreement
<PAGE>
                                                                             S-2

                                        LENDERS
                                        -------

                                        UNION BANK OF CALIFORNIA, N.A.

                                        By
                                          -----------------------------------
                                          Name:
                                          Title:

                                        WELLS FARGO BANK,  N.A.

                                        By
                                          -----------------------------------
                                          Name:
                                          Title:

                                        BANK ONE, NA

                                        By
                                          -----------------------------------
                                          Name:
                                          Title:

                                        BNP PARIBAS

                                        By
                                          -----------------------------------
                                          Name:
                                          Title:

                                        By
                                          -----------------------------------
                                          Name:
                                          Title:

                                        MELLON BANK, N.A.

                                        By
                                          -----------------------------------
                                          Name:
                                          Title:

           Signature Page to Amendment No. 1 to SPPC Credit Agreement
<PAGE>
                                                                             S-3

                                        BAYERISCHE LANDESBANK
                                        GIROZENTRALE

                                        By
                                          -----------------------------------
                                          Name:
                                          Title:

                                        By
                                          -----------------------------------
                                          Name:
                                          Title:

                                        MIZUHO CORPORATE BANK, LTD., formerly
                                        known as The Industrial Bank of Japan,
                                        Limited

                                        By
                                          -----------------------------------
                                          Name:
                                          Title:

                                        LEHMAN COMMERCIAL PAPER INC.

                                        By
                                          -----------------------------------
                                          Name:
                                          Title:

                                        WACHOVIA BANK, NATIONAL ASSOCIATION,
                                        formerly known as First Union National
                                        Bank

                                        By
                                          -----------------------------------
                                          Name:
                                          Title:

           Signature Page to Amendment No. 1 to SPPC Credit Agreement
<PAGE>
                                                                             S-4

                                        MERRILL LYNCH BANK USA

                                        By
                                          -----------------------------------
                                          Name:
                                          Title:

           Signature Page to Amendment No. 1 to SPPC Credit Agreement
<PAGE>
                                   EXHIBIT E
                                   ---------

                          PROJECTED/ACTUAL CASH FLOWS

                                   [ table ]<PAGE>
                                                                    Exhibit 10.1

               AMENDED AND RESTATED REGISTRATION RIGHTS AGREEMENT

         This Agreement is made and entered into as of this 12th day of August,
1998, by and among The Medicines Company, a Delaware corporation (the
"Company"), the individuals and entities listed on SCHEDULE I hereto (the "Old
Investors") and the individuals and entities listed on SCHEDULE II hereto (the
"New Investors"). The Old Investors and the New Investors are collectively
referred to herein as the "Investors".

         WHEREAS, the Company has previously entered into Stock Purchase
Agreements dated September 5, 1996, June 4, 1997 and December 17, 1997,
respectively (the "Old Stock Purchase Agreements") with the Old Investors; and

         WHEREAS, the Company and the Old Investors in connection with the Old
Stock Purchase Agreements, previously entered into a Registration Rights
Agreement dated June 4, 1997, as amended on December 17, 1997 (the "Registration
Rights Agreement"); and

         WHEREAS, the Company and the New Investors have entered into a Stock
Purchase Agreement dated as of August 12, 1998 (the "Purchase Agreement"), and

         WHEREAS, the Company and the Old Investors believe it to be in their
mutual best interests to amend and restate the Registration Rights Agreement;
and

         WHEREAS, the Company and the Investors desire to provide for certain
arrangements with respect to the registration of shares of capital stock of the
Company under the Securities Act of 1933, as amended; and

         NOW, THEREFORE, in consideration of the mutual promises and covenants
contained in this Agreement, the parties hereto agree to amend and restate the
Registration Rights Agreement as follows:

1.       DEFINITIONS.

         As used in this Agreement, the following terms shall have the following
meanings:

         (a) the term "Common Stock" means the common stock, $0.001 par value
per share, of the Company;

         (b) the term "Exchange Act" means the Securities Act of 1934, as
amended, or any similar Federal statute, and the rules and regulations of the
SEC Issued under such Act, as they each may, from time to time, be in effect;

         (c) the term "Holder" shall mean any holder of Registrable Securities;

         (d) the term "Initial Public Offering" means the initial underwritten
public offering of equity securities of the Company pursuant to an effective
Registration Statement;

         (e) the term "Initiating Holder" shall mean (i) any Holder or Holders
who in the aggregate are holders of more than 50% of the then outstanding
Registrable Securities, PROVIDED, that as to one (1) of the three (3) requested
registrations covered by Section 2 of this Agreement, Holders requesting
registration shall be deemed to constitute "Initiating Holders" only if such
Holders include Warburg, Pincus Ventures, L.P. ("Warburg"), and as to one (1) of
the three (3) requested registrations covered by Section 2 of this Agreement,

<PAGE>

Holders requesting such registration shall be deemed to constitute "Initiating
Holders" only if such Holders include Biotech Target, S.A. ("Biotech Target"),
and (ii) additionally, commencing three (3) years after the date hereof, New
Investors who in the aggregate are Holders of more than 20% of the shares of
Common Stock issued or issuable upon conversion of the Series III Convertible
Preferred Stock of the Company, par value $1.00 per share (the "Series III
Preferred Stock");

         (f) the terms "register," "registered" and "registration" refer to a
registration effected by preparing and filing a Registration Statement (and any
post-effective amendments filed or required to be filed) in compliance with the
Securities Act and the declaration or ordering of effectiveness of such
Registration Statement;

         (g) the term "Registrable Securities" means (1) any shares of Common
Stock issued or issuable on conversion of the Series III Preferred Stock and the
Series I Convertible Preferred Stock and Series II Convertible Preferred Stock,
each $1.00 par value per share (collectively, the "Preferred Stock"), (ii) any
additional shares of Common Stock acquired by the Investors, excluding shares
acquired by each of Clive A. Meanwell, Peyton Marshall, Wendy Gordon, John
Villiger, Thomas Lategan and Helmut Glersiefen pursuant to the Restricted Stock
Purchase Agreements, and (iii) any capital stock of the Company issued as a
dividend or other distribution with respect to, or in exchange for or in
replacement of, the shares of Common Stock referred to in clause (i), (ii) or
(iii);

         (h) "Registration Expenses" shall mean, with respect to any
registration, all expenses incurred by the Company in compliance with Sections 2
and 3 hereof, including, without limitation, all registration, qualification and
filing fees, printing expenses, fees and disbursements of counsel for the
Company, fees and expenses of one counsel for all the Holders in an amount not
to exceed $25,000 for each such registration (which counsel shall be selected by
Holders owning a majority of the Registrable Securities proposed to be included
in such registration), blue sky fees and expenses (including reasonable fees and
disbursements of a qualified independent underwriter, if any, counsel in
connection therewith and the reasonable fees and disbursements in connection
with blue sky qualifications) and the expense of any regular or special audits
incident to or required by any such registration (but excluding the compensation
of regular employees of the Company, which shall be paid in any event by the
Company), expenses of any comfort letters or costs associated with the delivery
by independent certified public accountants of a comfort letter or comfort
letters, fees and expenses of any special experts retained by the Company in
connection with such registration and fees and expenses of listing the
Registrable Securities on a securities exchange (including reasonable fees and
expenses of underwriter's counsel in connection therewith);

         (i) the term "Registration Statement" means a registration statement
filed by the Company with the SEC for a public offering and sale of Common Stock
(other than a registration statement on Form S-8 or Form S-4, or any other form
for a similar limited purpose, or any registration statement covering only
securities proposed to be issued in exchange for securities or assets of another
corporation);

         (j) "Restricted Stock Purchase Agreements" shall mean the respective
Stock Restriction Agreements between the Company and each of the following: (i)
Clive A. Meanwell dated as of September 5, 1996, (ii) Peyton Marshall dated as
of October 20, 1997, (iii) Wendy Gordon dated as of November 1, 1997, (iv) John
Villiger dated as of March 10, 1997, (v) Thomas Lategan dated as of February 24,
1997, and (vi) Helmut Giersiefen dated as of November 1, 1996 and as amended and
restated on April 4, 1997;

<PAGE>

         (k) the term "SEC" means the Securities and Exchange Commission, or any
other Federal Agency at the time administering the Securities Act;

         (l) the term "Securities Act" means the Securities Act of 1933, as
amended, or any similar federal statute, under the rules and regulations of the
SEC issued under such Act, as they each may, from time to time, be in effect;

         (m) "Selling Expenses" shall mean, with respect to any registration,
all underwriting discounts and selling commissions and stock transfer taxes
applicable to the sale of Registrable Securities and all fees and disbursements
of counsel for each of the Holders other than fees and expenses of one counsel
for all the Holders in an amount not to exceed $25,000 for such registration;
and

         (n) "Stockholders' Agreement" means the Third Amended and Restated
Stockholders' Agreement among the Investors, the Company and certain other
stockholders dated as of the date of this Agreement.

2.       REQUESTED REGISTRATION.

         (a) REQUEST FOR REGISTRATION. If the Company shall receive from an
Initiating Holder at any time or times a written request that the Company effect
any registration with respect to all or a part of the Registrable Securities,
the Company will:

         (i) promptly give written notice of the proposed registration to all
         other Holders of Registrable Securities; and

         (ii) as soon as practicable, use its diligent best efforts to effect
         such registration (including, without limitation, the execution of an
         undertaking to file post-effective amendments, appropriate
         qualification under applicable blue sky or other state securities laws
         and appropriate compliance with applicable regulations issued under the
         Securities Act) as may be so requested and as would permit or
         facilitate the sale and distribution of all or such portion of such
         Registrable Securities as are specified in such request, together with
         all or such portion of the Registrable Securities of any Holder or
         Holders joining in such request as are specified in a written request
         received by the Company within ten (10) business days after written
         notice from the Company is given under Section 2(a)(1) above; provided
         that the Company shall not be obligated to effect, or take any action
         to effect, any such registration pursuant to this Section 2:

                  A. In any particular jurisdiction in which the Company would
                  be required to execute a general consent to service of process
                  in effecting such registration, qualification or compliance,
                  unless the Company is already subject to service in such
                  jurisdiction and except as may be required by the Securities
                  Act or applicable rules or regulations thereunder;

                  B. After the Company has effected three (3) such registrations
                  pursuant to this Section 2 requested by Initiating Holders
                  described in clause (i) of the definition thereof and two (2)
                  such registrations requested by Initiating Holders described
                  in clause (ii) of the definition thereof, and such
                  registrations have been declared or ordered effective and the
                  sales of such Registrable Securities shall have closed;

<PAGE>

                  C. (i) In the case of any registration requested by Initiating
                  Holders described in clause (i) of the definition thereof, if
                  the Registrable Securities requested by all Holders to be
                  registered pursuant to such request do not have, in the good
                  faith judgment of the Board of Directors of the Company, an
                  anticipated aggregate public offering price (before any
                  underwriting discounts and commissions) of at least $5,000,000
                  (or $10,000,000 if such requested registration is the Initial
                  Public Offering) and, as to the Initial Public Offering, if
                  the request is not made by Holders who in the aggregate hold
                  at least sixty-five percent (65%) of the Registrable
                  Securities;

                           (ii) In the case of any registration requested by
                           Initiating Holders described in clause (ii) of the
                           definition thereof, the Registrable Securities
                           requested by such Initiating Holders to be registered
                           do not constitute at least 15% of the Common Stock
                           issued or issuable upon conversion of the Series III
                           Preferred Stock or do not have, in the good faith
                           judgment of the Board of Directors of the Company, an
                           anticipated aggregate public offering price (before
                           any underwriting discounts and commissions) of at
                           least $5,000,000 (or $10,000,000 if such requested
                           registration is in the Initial Public Offering); or

                  D. If at the time of any request to register Registrable
                  Securities pursuant to this Section 2, the Company is engaged
                  or has fixed plans to engage within thirty (30) days of the
                  time of the request in a registered public offering as to
                  which the Holders may include Registrable Securities pursuant
                  to Section 3 or is engaged in any financing, acquisition or
                  other material transaction which, in the good faith
                  determination of the Board of Directors of the Company, would
                  be adversely affected by the requested registration to the
                  material detriment of the Company, then the Company may,, at
                  its option, direct that such request be delayed for the
                  shortest reasonable period of time not in excess of 120 days
                  from the date of such request, such right to delay a request
                  to be exercised by the Company not more than once in any
                  one-year period. In any such event, the Company shall promptly
                  give the Holders written notice of such determination,
                  containing a general statement of the reasons for such
                  postponement and an approximation of the anticipated delay. If
                  the Company shall so postpone the filing of the Registration
                  Statement, the Holders who made the request for registration
                  shall have the right to withdraw the request for registration
                  by giving written notice to the Company within thirty (30)
                  days after receipt of the notice of postponement.

         The Registration Statement filed pursuant to the request of any of the
Initiating Holders may, subject to the provisions of Section 2(b) below, include
other securities of the Company or which are held by Persons who, by virtue of
agreements with the Company, are entitled to include their securities in any
such registration, provided that such Persons shall be subject to the provisions
of Section 2(b) below.

         The Initiating Holders that made the registration request may, at any
time prior to the effective date of the Registration Statement relating to such
registration revoke such request, without liability to any other party, by
providing a written notice to the Company revoking such request.

<PAGE>

         (b) UNDERWRITING. If the Initiating Holders intend to distribute the
Registrable Securities covered by their request by means of an underwriting,
they shall so advise the Company as a part of their request made pursuant to
Section 2.

         If holders of securities of the Company other than Registrable
Securities who are entitled, by contract with the Company or otherwise, to have
securities included in such a registration (the "Other Stockholders") request
such inclusion, the Holders shall offer to include the securities of such Other
Stockholders in the underwriting and may condition such offer on their
acceptance of the further applicable provisions of this Agreement. The Holders
whose shares are to be included in such registration and the Company shall
(together with all Other Stockholders proposing to distribute their securities
through such underwriting) enter into an underwriting agreement in customary
form with the representative of the underwriter or underwriters selected for
such underwriting by the Initiating Holders holding a majority of Registrable
Securities held by the Initiating Holders and reasonably acceptable to the
Company and the price, terms and provisions of the underwriting and the offering
shall be subject to the approval of the Company and such Initiating Holders. Any
affiliate of a Holder may be selected to serve, on an arm's-length basis, as
underwriter for an underwritten offering effected pursuant to this Section 2(b).
Notwithstanding any other provision of this Section 2, if the representative
advises the Holders in writing that marketing factors require a limitation on
the number of shares to be underwritten, the securities of the Company held by
Other Stockholders shall be excluded from such registration to the extent so
required by such limitation. If, after the exclusion of such shares, further
reductions are still required, the number of shares included in the registration
by each Holder shall be reduced on a pro rata basis (based on the number of
shares requested to be included by such Holder), by such minimum number of
shares as is necessary to comply with such request. No Registrable Securities or
any other securities excluded from the underwriting by reason of the
underwriter's marketing limitation shall be included in such registration. If at
least 50% of the Registrable Securities requested to be included in such
registration by the Initiating Holders are excluded by reason of the
underwriter's marketing limitation, the registration shall not be counted for
purposes of paragraph (B) of Section 2(a)(ii). If any of the Holders or any
Other Stockholder who has requested inclusion in such registration as provided
above disapproves of the terms of the underwriting, such person may elect to
withdraw therefrom without liability to any party by written notice to the
Company, the underwriter and the Initiating Holders. The securities so withdrawn
shall also be withdrawn from registration. If the underwriter has not limited
the number of Registrable Securities to be underwritten, the Company may include
its securities for its own account in such registration if the representative so
agrees and if the number of Registrable Securities which would otherwise have
been included in such registration and underwriting will not thereby be limited.

3.       COMPANY REGISTRATION.

         (a) INCLUSION IN REGISTRATION. If the Company shall determine to
register any of its equity securities either for its own account or for the
account of a security holder or holders exercising their respective demand
registration rights (including any such registration pursuant to Section 4, but
excluding any such registration pursuant to Section 2), other than a
registration relating solely to employee benefit plans, or a registration
relating solely to a SEC Rule 145 transaction, or a registration on any
registration form which does not permit secondary sales, the Company will:

         (i) promptly (but in any event at least 15 days prior to the
         anticipated filing date) give to each of the Holders a written notice
         thereof (which shall include a list of the

<PAGE>

         jurisdictions in which the Company intends to attempt to qualify such
         securities under the applicable blue sky or other state securities
         laws); and

         (ii) include in such registration (and any related qualification under
         blue sky laws or other compliance), and in any underwriting involved
         therein, all the Registrable Securities specified in a written request
         or requests, made by any Holder within fifteen (15) days after receipt
         of the written notice from the Company described in clause (1) above,
         except as set forth in Section 3(b) below. Such written request may
         specify all or a part of a Holder's Registrable Securities.

         (b) UNDERWRITING. If the registration of which the Company gives notice
is for a registered public offering involving an underwriting, the Company shall
so advise each of the Holders as a part of the written notice given pursuant to
Section 3(a)(i). In such event, the right of each of the Holders to registration
pursuant to this Section 3 shall be conditioned upon such Holder's participation
in such underwriting and the inclusion of such Holder's Registrable Securities
in the underwriting to the extent provided herein. The Holders whose shares are
to be included in such registration shall (together with the Company and the
Other Stockholders distributing their securities through such underwriting)
enter into an underwriting agreement in customary form with the representative
of the underwriter or underwriters selected for underwriting by the Company.
Notwithstanding any other provision of this Section 3, if the representative
determines that marketing factors require a limitation on the number of shares
to be underwritten, and (x) if such registration is the Initial Public Offering,
the representative may, subject to the allocation priority set forth below,
exclude from such registration and underwriting all of the Registrable
Securities which would otherwise be underwritten pursuant hereto, and (y) if
such registration is other than the Initial Public Offering, the representative
may (subject to the allocation priority set forth below) limit the number of
Registrable Securities to be included in the registration and underwriting to
not less than twenty-five percent (25%) of the securities included therein. The
Company shall so advise all holders of securities requesting registration, and
the number of shares of securities that are entitled to be included in the
registration and underwriting shall be allocated in the following manner: The
securities of the Company held by Other Stockholders of the Company (other than
Registrable Securities, if any are held by such Other Stockholders, and other
than securities held by holders (other than Holders) who by contractual right
demanded such registration ("Demanding Holders")) shall be excluded from such
registration and underwriting to the extent required by such limitation, and, if
a limitation on the number of shares is still required, the number of shares
that may be included in the registration and underwriting by each of the Holders
and the Demanding Holders shall be reduced, on a pro rata basis (based on the
number of shares requested to be included by such Holder), by such minimum
number of shares as is necessary to comply with such limitation. If any of the
Holders or any Other Stockholder disapproves of the terms of any such
underwriting, such person may elect to withdraw therefrom without liability to
any party by written notice to the Company and the underwriter. Any Registrable
Securities or other securities excluded or withdrawn from such underwriting
shall be withdrawn from such registration.

         (c) No registration effected under this Section 3 shall relieve the
Company of its obligation to effect any registration upon request under Section
2 or Section 4, except as otherwise provided herein.

4.       FORM S-3.

<PAGE>

         Following the Initial Public Offering the Company shall use its best
efforts to qualify for registration on Form S-3 (or any equivalent successor
form) for secondary sales. After the Company has qualified for the use of Form
S-3, Holders of Registrable Securities shall have the right to request up to
nine (9) registrations on Form S-3 (one of which may be exercised by War6urg,
one of which may be exercised by Biotech Target, one of which may be exercised
by PharmaBio Development, Inc. ("PharmaBio"), one of which may be exercised by
the MPM Group (as defined in the Stockholders' Agreement)) and five (5) of which
may be exercised by New Investors holding a majority of Registrable Securities
held by all of the New Investors (such requests shall be `in writing and shall
state the number of shares of Registrable Securities to be disposed of and the
intended method of disposition of shares by such Holders), subject only to the
following:

         (i) The Company shall not be required to effect a registration pursuant
         to this Section 4 unless the Holder or Holders of Registrable
         Securities requesting registration propose to dispose of shares of
         Registrable Securities that are expected to have an aggregate price to
         the public (before deduction of underwriting discounts and expenses of
         sale) of more than $3,000,000.

         (ii) The Company shall not be required to effect a registration
         pursuant to this Section 4 within 180 days of the effective date of the
         most recent registration pursuant to this Section 4 in which securities
         held by the requesting Holder could have been included for sale or
         distribution.

         (iii) The Company shall not be required to effect a registration
         pursuant to this Section 4 in any particular jurisdiction in which the
         Company would be required to execute a general consent to service of
         process in effecting such registration, qualification or compliance,
         unless the Company is already subject to service in such jurisdiction
         and except as may be required by the Securities Act or applicable rules
         or regulations thereunder.

         (iv) If at the time of any request to register Registrable Securities
         pursuant to this Section 2, the Company is engaged or has fixed plans
         to engage within thirty (30) days of the time of the request in a
         registered public offering as to which the Holders may include
         Registrable Securities pursuant to Section 3 or is engaged in any
         financing, acquisition or other material transaction which, in the good
         faith determination of the Board of Directors of the Company, would be
         adversely affected by the requested registration to the material
         detriment of the Company, then the Company may, at its option, direct
         that such request be delayed for the shortest reasonable period of time
         not in excess of 120 days from the date of such request, such right to
         delay a request to be exercised by the Company not more than once in
         any one-year period. In any such event, the Company shall promptly give
         the Holders written notice of such determination, containing a general
         statement of the reasons for such postponement and an approximation of
         the anticipated delay.

         The Company shall give prompt written notice to all Holders of
Registrable Securities of the receipt of a request for registration pursuant to
this Section 4 and as soon as practicable, use its diligent best efforts to
effect such registration (including, without limitation, the execution of an
undertaking to file post-effective amendments, appropriate qualification under
applicable blue sky or other state securities laws and appropriate compliance
with applicable regulations issued under the Securities Act) as may be so
requested and as would permit or facilitate the sale and distribution of all or
such portion of

<PAGE>

such Registrable Securities as are specified in such request, together with all
or such portion of the Registrable Securities of any Holder or Holders joining
in such request as are specified in a written request received by the Company
within ten (10) business days after written notice from the Company is given;
provided that if the registration is for an underwritten offering, the terms of
Section 2(b) shall apply to all participants in such offering. Subject to the
foregoing, the Company will use its best efforts to effect promptly the
registration of all shares of Registrable Securities on Form S-3 to the extent
requested by the Holder or Holders thereof for purposes of disposition.

5.       EXPENSES OF REGISTRATION.

         All Registration Expenses incurred in connection with any registration,
qualification or compliance that is proposed or effected pursuant to this
Agreement shall be borne by the Company, and all Selling Expenses shall be borne
by the Holders of the securities so registered pro rata on the basis of the
number of their shares so registered; provided, however, that the Company shall
not be required to pay any Registration Expenses in the event the Registration
Statement is withdrawn at the request of the Initiating Holders (other than as a
result of information concerning the business or financial condition of the
Company which is made known to the Initiating Holders after the date on which
such registration was requested if such withdrawal occurs within 10 days of the
Initiating Holders becoming aware of such information) and each of the
Initiating Holders agrees to bear such Registration Expenses pro rata on the
basis of the number of their shares so included in the registration request (or
on some other basis as they may agree), in which case such registration shall
not be counted as a registration pursuant to Section 2(a)(ii)(B) or 4. In the
event that the Registration Statement is withdrawn and the Initiating Holders
requesting registration fail to pay the expenses as provided in the immediately
preceding sentence, such registration shall be counted as a registration
pursuant to Section 2(a)(ii)(B) or 4.

6.       REGISTRATION PROCEDURES.

         In the case of each registration effected by the Company pursuant to
this Agreement, the Company will keep the Holders, as applicable, advised in
writing of the effectiveness thereof and of any stop order issued or, to the
Company's knowledge, threatened by the SEC and take all reasonable actions
required to prevent the entry of such stop order or to remove it if entered and
promptly notify such Holder of such lifting or withdrawal of such order. At its
expense, the Company will:

         (i) prepare and file with the SEC such amendments and supplements to
         such Registration Statement and the prospectus used in connection
         therewith as may be necessary to keep such Registration Statement
         effective for the period specified in Section 6(vi) and to comply with
         the provisions of the Securities Act with respect to the disposition of
         all securities covered by such Registration Statement during such
         period; provided that the Company will, to the extent practicable, at
         least three days prior to filing a Registration Statement or prospectus
         or any amendment or supplement thereto, furnish to each Holder copies
         of such Registration Statement or prospectus (or amendment or
         supplement) as proposed to be filed (including, upon the request of
         such Holder, documents to be incorporated by reference therein) which
         documents will be subject to the reasonable review and comments of such
         Holder and counsel for the Holders, which review will be completed as
         expeditiously as possible; and the Company will not include any
         statement in any Registration Statement or prospectus (or amendment or
         supplement) with respect to such Holder to which such

<PAGE>

         Holder shall reasonably object in writing except as may be required to
         comply with securities laws and disclosure obligations thereunder;

         (ii) furnish to each Holder and to each underwriter, if any, a signed
         counterpart of: (x) an opinion of counsel for the Company addressed to
         such Holder and underwriter on which opinion such Holder and
         underwriter is entitled to rely, and (y) a "comfort" letter signed by
         the independent public accountants who have certified the Company's
         financial statements included in such Registration Statement, each in
         customary form and covering such matters of the type customarily
         covered by opinions or comfort letters, as the case may be, as the
         managing underwriter therefor reasonably request;

         (iii) immediately notify each Holder at any time when a prospectus
         relating thereto is required to be delivered under the Securities Act,
         upon discovery that, or upon the happening of any event as a result of
         which, the prospectus included in such Registration Statement, as then
         in effect, includes an untrue statement of a material fact or omits to
         state any material fact required to be stated therein or necessary to
         make the statements therein not misleading in the light of the
         circumstances under which they were made, and promptly prepare and
         furnish to such Holder a reasonable number of copies of any supplement
         to or amendment of such prospectus as may be necessary so that, as
         thereafter delivered to the purchasers of such securities, such
         prospectus shall not include an untrue statement of a material fact or
         omit to state a material fact required to be stated therein or
         necessary to make statements therein not misleading in the light of the
         circumstances under which they were made;

         (iv) make available for inspection by any Holder, any underwriter
         participating in any disposition pursuant to such Registration
         Statement and any attorney, accountant or other professional retained
         by any such Holder or underwriter, all financial and other records,
         pertinent corporate documents and properties of the Company as shall be
         reasonably necessary to enable them to exercise their due diligence
         responsibility;

         (v) otherwise use its reasonable best efforts to list all Registrable
         Securities covered by such Registration Statement on any securities
         exchange or I quotation system on which any of the Registrable
         Securities is then listed or traded; to cause all Registrable
         Securities covered by such Registration Statement to be registered with
         or approved by such other governmental agencies or authorities as may
         be necessary to enable the Holders to consummate the disposition of
         such Registrable Securities; to comply with all applicable rules and
         regulations of the SEC, and make available to its securityholders, as
         soon as reasonably practicable, an earnings statement covering the
         period of at least twelve (12) months beginning with the first full
         calendar month of the Company first fiscal quarter commencing after the
         effective date of such Registration Statement, which earnings statement
         shall satisfy the provisions of Section 11(a) of the Securities Act and
         Rule 158 thereunder;

         (vi) keep such registration effective for a period of 120 days or until
         the Holders, as applicable, have completed the distribution described
         in the Registration Statement relating thereto, whichever first occurs;
         provided, however, that (A) in the event such Holders are required to
         refrain from selling securities pursuant to a separate registration
         during such 120-day period pursuant to Section 10 hereof, such 120-day
         period shall be extended for a period of time equal to the period
         during which the Holders refrain from selling any securities in
         accordance with provisions in Section 10 hereof; and in the case of any
         registration of Registrable Securities on Form S-3

<PAGE>

         which are intended to be offered on a continuous or delayed basis, such
         120-day period shall be extended until all such Registrable Securities
         are sold, provided that Rule 415, or any successor rule under the
         Securities Act, permits an offering on a continuous or delayed basis,
         and provided further that applicable rules under the Securities Act
         governing the obligation to file a post-effective amendment permit, in
         lieu of filing a post-effective amendment which (y) includes any
         prospectus required by Section 10(a) of the Securities Act or (z)
         reflects facts or events representing a material or fundamental change
         in the information set forth in the Registration Statement, the
         incorporation by reference of information required to be included in
         (y) and (z) above to be contained in periodic reports filed pursuant to
         Section 13 or 15(d) of the Exchange Act in the Registration Statement;
         and

         (vii) furnish such number of Registration Statements, prospectuses,
         amendments or supplements thereto and other documents incident thereto
         as each of the Holders, as applicable, from time to time may reasonably
         request.

7.       INDEMNIFICATION.

         (a) The Company will indemnify each of the Holders, as applicable, each
of its officers, directors, partners and agents, and each person controlling
each of the Holders within the meaning of Section 15 of the Securities Act or
Section 20 of the Exchange Act, with respect to each registration which has been
effected pursuant to this Agreement, and each underwriter, if any, and each
person who controls any underwriter, against all expenses, claims, losses,
damages and liabilities (or actions, proceedings or settlements in respect
thereof) arising out of or based on any untrue statement (or alleged untrue
statement) of a material fact contained in any prospectus, offering circular or
other document (including any related Registration Statement, notification or
the like), as amended or supplemented, incident to any such registration,
qualification or compliance, or based on any omission (or alleged omission) to
state therein a material fact required to be stated therein or necessary to make
the statements therein not misleading, or any violation by the Company of the
Securities Act, Exchange Act, state securities laws or any rule or regulation
thereunder applicable to the Company and relating to action or inaction required
of the Company in connection with any such registration, qualification or
compliance, and will reimburse each of the Holders, each of its officers,
directors, partners and agents, and each person controlling each of the Holders,
each such underwriter and each person who controls any such underwriter, for any
legal and any other expenses reasonably incurred in connection with
investigating, defending or settling any such claim, loss, damage, liability or
action, provided that the Company will not be liable in any such case to the
extent that any such claim, loss, damage, liability or expense arises out of or
is based on any untrue statement or omission based upon written information
furnished to the Company by the Holders or underwriter and stated to be
specifically for use therein, PROVIDED that the obligations of the Company
hereunder shall not apply to amounts paid in settlement of any such claim, loss,
damage, liability or action if such settlement is effected without the consent
of the Company.

         (b) Each of the Holders will, severally (in the proportion that the
proceeds of the offering received by such Holder bears to the total proceeds of
the offering received by all the Holders) and not jointly, if Registrable
Securities held by it are included in the securities as to which such
registration, qualification or compliance is being effected, indemnify the
Company, each of its directors and officers and each underwriter, if any, of the
Company's securities covered by such a Registration Statement, each person who
controls the Company or such underwriter against all claims, losses, damages and
liabilities (or actions in respect

<PAGE>

thereof) arising out of or based on any untrue statement (or alleged untrue
statement) of a material fact contained in any such Registration Statement,
prospectus, offering circular or other document made by such Holder, or any
omission (or alleged omission) to state therein a material fact required to be
stated therein or necessary to make the statements by such Holder therein not
misleading, and will reimburse the Company and such directors, officers,
partners, persons, underwriters or control persons for any legal or any other
expenses reasonably incurred in connection with investigating or defending any
such claim, loss, damage, liability or action, in each case to the extent, but
only to the extent, that such untrue statement (or alleged untrue statement) or
omission (or alleged omission) is made in such Registration Statement,
prospectus, offering circular or other document in reliance upon and in
conformity with written information furnished to the Company by such Holder and
stated to be specifically

<PAGE>

for use therein; provided, however, that (i) the obligations of each of the
Holders hereunder shall be limited to an amount equal to the net proceeds to
such Holder of securities sold as contemplated herein., and (ii) the obligations
of each of the Holders hereunder shall not apply to amounts paid in settlement
of any such claim, loss, damage, liability or action if such settlement is
effected without the consent of such Holder.

         (c) Each party entitled to indemnification under this Section 7 (the
"Indemnified Party") shall give written notice to the party required to provide
indemnification (the "Indemnifying Party") promptly after such Indemnified Party
has actual knowledge of any claim as to which indemnity may be sought, and shall
permit the Indemnifying Party to assume the defense of any such claim or any
litigation resulting therefrom; provided that counsel for the Indemnifying
Party, who shall conduct the defense of such claim or any litigation resulting
therefrom, shall be approved by the Indemnified Party (whose approval shall not
unreasonably be withheld) and the Indemnified Party may participate in such
defense at such party's expense (unless the Indemnified Party shall have
reasonably concluded that there may be a conflict of interest between the
Indemnifying Party and the Indemnified Party in such action, in which case the
fees and expenses of counsel shall be at the expense of the Indemnifying Party),
and provided further that the failure of any Indemnified Party to give notice as
provided herein shall not relieve the Indemnifying Party of its obligations
under this Agreement unless the Indemnifying Party is materially prejudiced
thereby. No Indemnifying Party, in the defense of any such claim or litigation
shall, except with the consent of each Indemnified Party, consent to entry of
any judgment or enter into any settlement which does not include as an
unconditional term thereof the giving by the claimant or plaintiff to such
Indemnified Party of a release from all liability in respect to such claim or
litigation. Each Indemnified Party shall furnish such information regarding
itself or the claim in question as an Indemnifying Party may reasonably request
in writing and as shall be reasonably required in connection with the defense of
such claim and litigation resulting therefrom. Any counsel representing the
Holders (as Indemnifying Party or Indemnified Party) shall be selected by the
holders holding a maj9rity of the Registrable Securities included in such
registration.

         (d) In order to provide for just and equitable contribution to joint
liability in any case in which either (i) any Indemnified Party exercising
rights under this Agreement makes a claim for indemnification pursuant to this
Section 7 but it is judicially determined (by the entry of a final judgment or
decree by a court of competent jurisdiction and the expiration of time to appeal
or the denial of the last right of appeal) that such indemnification may not be
enforced in such case notwithstanding the fact that this Section 7 provides for
indemnification in such case, or (ii) contribution under the Securities Act may
be required on the part of any such Indemnified Party in circumstances for which
indemnification Is provided under tills Section 71- then, and in each such case,
each Indemnifying Party and Indemnified Party will contribute to the aggregate
losses, claims, damages or liabilities to which they may be subject (after
contribution from others) in proportion-to the relative fault of the
Indemnifying Party, on the one hand, and each Indemnified Party, on the other
hand; PROVIDED HOWEVER that, in any such case, no person or entity guilty of
fraudulent misrepresentation (within the meaning of Section 11(f) of the
Securities Act) will be entitled to contribution from any person or entity who
was not guilty of such fraudulent misrepresentation and no such Indemnifying
Party will be required to contribute any amount in excess of the public offering
price of all shares sold by it pursuant to such registration statement. The
relative fault of each Indemnifying Party and of the Indemnified Party shall be
determined by reference to, among other things, whether the untrue or alleged
untrue

<PAGE>

statement of a material fact or the omission to state a material fact relates to
information supplied by the Indemnifying Party or by the Indemnified Party and
the parties' relative intent, knowledge, access to information, and opportunity
to correct or prevent such statement or omission. The Company and the Investors
agree that it would not be just and equitable if contribution pursuant to this
Section 7 were determined by pro rata allocation or by any other method of
allocation which does not take account of the equitable considerations referred
to above.

         (e) Notwithstanding the foregoing, to the extent that the provisions on
indemnification and contribution contained in the underwriting agreement entered
into in connection with any underwritten public offering contemplated by this
Agreement are in conflict with the foregoing provisions, the provisions in such
underwriting agreement shall be controlling.

         (f) The amount paid or payable by an Indemnified Party as a result of
the losses, claims, damages or liabilities referred to in this Section 7 shall
be deemed to include, subject to the limitations set forth above, any legal or
other expenses reasonably incurred by such Indemnified Party In connection with
investigating or defending any such action or claim in accordance with the
provisions hereof.

         (g) The foregoing indemnity agreement of the Company and the Holders is
subject to the condition that, insofar as they relate to any loss, claim,
liability or damage made in a preliminary prospectus but eliminated or remedied
in the amended prospectus on file with the SEC at the time the Registration
Statement in question becomes effective or the amended prospectus filed with the
SEC pursuant to SEC Rule 424(b) (the "Final Prospectus"), such indemnity
agreement shall not inure to the benefit of any Indemnified Party if a copy of
the Final Prospectus was furnished to the Indemnified Party, the Indemnified
Party was required by the Securities Act to furnish the Final Prospectus to the
person asserting the loss, liability, claim or damage and the Indemnified Party
did not so furnish the final Prospectus at or prior to the time such action is
required by the Securities Act.

8.       INFORMATION BY THE HOLDERS.

         Each of the Holders holding securities included in any registration
shall furnish to the Company such information regarding such Holder and the
distribution proposed by such Holder as the Company may reasonably request in
writing and as shall be reasonably required in connection with any registration,
qualification or compliance referred to in this Agreement.

9.       RULE 144 Reporting.

         (a) With a view to making available the benefits of certain rules and
regulations of the SEC which may permit the safe of restricted securities to the
public without registration, the Company agrees to:

         (i) make and keep public information available as those terms are
         understood and defined in Rule 144 of the Securities Act, at all times
         from and after ninety (90) days following the effective date of the
         first registration under the Securities Act filed by the Company for an
         offering of its securities to the general public;

<PAGE>

         (ii) use its best efforts to file with the SEC in a timely manner all
         reports and other documents required of the Company under the
         Securities Act and the Exchange Act at any time after it has become
         subject to such reporting requirements; and

         (iii) so long as the Holder owns any Registrable Securities, furnish to
         the Holder upon request, a written statement by the Company as to its
         compliance with the reporting requirements of Rule 144 (at any time
         from and after ninety (90) days following the effective date of the
         first Registration Statement filed by the Company for an offering of
         its securities to the general public), and of the Securities Act and
         the Exchange Act (at any time after it has become subject to such
         reporting requirements), a copy of the most recent annual or quarterly
         report of the Company, and such other reports and documents so filed as
         the Holder may reasonably request in availing itself of any rule or
         regulation of the SEC allowing the Holder to sell any such securities
         without registration.

10.      "MARKET STAND-OFF" AGREEMENT.

         Each of the Holders agrees, if requested by the Company and an
underwriter of Common Stock (or other securities) of the Company at least five
(5) business days prior to the anticipated beginning of the period referred to
below, not to sell or otherwise transfer or dispose of any Common Stock (or
other securities) of the Company held by such Holder (1) for a period of 180
days in the case of the "Initial Public Offering (except as part of such
offering), and (ii) for a period of 120 days in the case of any offering of
shares of Common Stock other than the Initial Public Offering (except as part of
such offering), in each case following the effective date of a Registration
Statement of the Company filed under the Securities Act, provided that:

         (a) the provisions of this Section-10 shall apply to the Initial Public
Offering and to any Registration Statement filed within two (2) years of the
Company's Initial Public Offering; and

         (b) all officers and directors of the Company and any entities with
which an officer or director is an affiliate which holds securities of the
Company enter into and are bound by similar agreements.

         If requested by the underwriters, the Holders shall execute a separate
agreement to the foregoing effect. The Company may impose stop-transfer
instructions with respect to the shares (o securities) subject to the foregoing
restriction until the end of said 180- t 120-day period, as the case may be. The
provisions of this Section 10 shall be binding upon any transferee who acquires
Registrable Securities, whether or not such transferee is entitled to the
registration rights provided hereunder.

         The Company agrees, if requested, by an underwriter of Common Stock (or
other securities) of the Company in connection with an underwriting hereby, that
(1) it will not effect any sale or distribution of any of its equity securities
or of any security convertible into or exchangeable or exercisable for any
equity security of the Company during the period of 120 days (or 180 days, "in
the case of the Initial Public Offering) beginning on the effective date of a
Registration Statement of the Company filed under the Securities Act without the
written consent of such managing underwriter, other than Common Stock (or other
securities) of the Company being sold, transferred or disposed of (A) pursuant
to such Registration Statement or any other registration requested hereby, (B)
pursuant to any of the Company's

<PAGE>

stock plans, (C) in connection with the conversion or exercise of any liens
outstanding securities of the Company, (D) in connection with any collaborative
or licensing arrangement, distribution arrangement or loan facility and (E) in
connection with the acquisition of another entity or assets of another entity by
the Company, and (1i) any agreement entered into after the date of this
Agreement pursuant to which the Company issues or agrees to issue any privately
placed securities shall contain a provision under which holders of such
securities agree not to effect any sale or distribution of any such securities
during the periods described in (1) above (except as part of any such
registration, if permitted).

11.      TERMINATION.

         The registration rights set forth in this Agreement shall not be
available to any Holder IF, IN THE WRITTEN OPINION OF REGULAR, OUTSIDE COUNSEL
TO THE Company, all of the Registrable Securities then owned by such Holder
could be sold in any ninety (90) day period pursuant to Rule 144 under the
Securities Act (without giving effect to the provisions of Rule 144 (k)).

12.      CHANGES IN COMMON STOCK OR PREFERRED STOCK.

         If, and as often as, there is any change in, exchange for or
substitution of the Common Stock or the Preferred Stock by reason of any
reorganization, recapitalization, reclassification, merger, consolidation,
spin-off, partial or complete liquidation, stock dividend, split-up, sale of
assets, distribution to stockholders or combination of the Company's securities
or other similar change in the capital structure of the Company, appropriate
adjustment shall be made in the provisions hereof so that the rights and
privileges granted hereunder shall continue with respect to the Registrable
Securities as so changed.

13.      NOTICES.

         (a) Alt communications under this Agreement shall be in writing and
shall be delivered by hand or mailed by overnight courier or by registered mail
or certified mail, postage prepaid:

         (i) if to an Investor listed on SCHEDULE I hereto, at his, her or its
         address set forth in SCHEDULE I, or at such other address as may have
         been furnished to the Company in writing; or

         (ii) if to an Investor listed on SCHEDULE II hereto, at his, her or its
         address set forth on SCHEDULE II, or at such other address as may have
         been furnished to the Company in writing; or

         (iii) if to the Company, at One Cambridge Center, Cambridge,
         Massachusetts 02142, marked for the attention of Clive A. Meanwell, or
         at such other address as the Company may have furnished in writing to
         the Investors, with a copy (which shall not constitute notice) to Hale
         and Dorr LLP, 60 State Street, Boston, Massachusetts 02109,1 marked for
         the attention of Steven D. Singer, Esq.

         (b) Any notice so addressed shall be deemed to be given: if delivered
by hand, on the date of such delivery; if mailed by courier, on the first
business day following the date of such malting; and if mailed by registered or
certified mail, on the third business day after the date of such mailing.

<PAGE>

14.      SUCCESSORS AND ASSIGNS.

         The registration rights set forth in this Agreement shall be assignable
by any Investor, in whole or in part, to any transferee of Registrable
Securities who (i) beneficially owns at least 1% of the outstanding Common Stock
(calculated on an as-converted basis)(within the meaning of Rule 13d-3 under the
Exchange Act) or (ii) acquires 100% of the Registrable Securities owned by the
transferring Investor on the date of such assignment; provided that any such
transferee shall agree in writing to be bound by the obligations of the
Investors under this Agreement. The provisions of this Agreement shall be
binding upon and accrue to the benefit of the parties hereto and their
respective heirs, executors, administrators, successors and permitted assigns;
provided that the Company may not transfer or assign any of its rights or
obligations under this Agreement. Nothing in this Agreement, express or implied,
is intended to confer on any Person other than the parties hereto, and their
respective successors and permitted assigns, any rights, remedies, obligations
or liabilities under or by reason of this Agreement.

15.      TERMINATION OF THE REGISTRATION RIGHTS AGREEMENT.

         Upon the effectiveness of this Agreement, the Registration Rights
Agreement is terminated and shall be superseded by the provisions of this
Agreement.

16.      ENTIRE AGREEMENT; AMENDMENT AND WAIVER.

         This Agreement constitutes the entire understandings of the parties
hereto and supersedes all prior agreements or understandings with respect to the
subject matter hereof among such parties. This Agreement may be amended, and the
observance of any term of this Agreement may be waived, with (and only with) the
written consent of the Holders of at least seventy-five percent (75%) of the
Registrable Securities.

17.      LIMITATION ON ENFORCEMENT OF REMEDIES.

         The Company hereby agrees that it will not assert against the limited
partners of any of the Investors any claim it may have under this Agreement by
reason of any failure or alleged failure by such Investor to meet its
obligations hereunder.

18.      GOVERNING LAW.

         This Agreement shall be construed in accordance with and governed by
the laws of the State of Delaware, without regard to the conflicts of law
principles thereof. Counterparts.

         This Agreement may be executed in one or more counterparts, each of
which shall be deemed an original and all of which together shall be considered
one and the same agreement.

19.      REMEDIES.

         The parties hereto acknowledge and agree that in the event of any
breach of this Agreement, the parties could be irreparably harmed and could not
be made whole by monetary damages. Each party hereto accordingly agrees (i) not
to assert by way of defense or otherwise that a remedy at law would be adequate,
and (ii) that the parties agree, in addition to any other remedy to which they
may be entitled, that the parties may seek the remedy of specific performance of
this Agreement, if appropriate, in any action in court.

<PAGE>

         IN WITNESS WHEREOF, the parties hereto have executed this Registration
Rights Agreement as of the date first above written.

                                 THE MEDICINES COMPANY

                                 By: /s/ Peyton J. Marshall
                                    ----------------------------------------
                                 Name: Peyton J. Marshall
                                 Title: Chief Financial Officer

                                 OLD INVESTORS:

                                 Holders of at least 75% of the Registrable
                                 Securities

                                 By: /s/ Peyton J. Marshall
                                    ----------------------------------------
                                    Under Power of Attorney of Holders
                                    attached hereto

                                 NEW INVESTORS:

                                 Counterpart signature pages attached hereto

<PAGE>

                                   SCHEDULE I

Warburg, Pincus Ventures, L.P.
466 Lexington Avenue
New York, New York 10017

MPM Medicines L.P.
One Cambridge Center
Cambridge, Massachusetts 02142

Hanseatic Americas LDC
450 Park Avenue
Suite 2302
New York, New York 10022

PharmaBio Development Inc.
Post Office Box 13979
Research Triangle Park, North Carolina 27709-3979

Biotech Target, S.A
c/o Bellevue Asset Management AG
Grafenauweg 4 P.  0.  Box CH-6301 Zug, Switzerland

Helmut Giersiefen
The Medicines Company
One Cambridge Center
Cambridge, Massachusetts 02142

John Villiger
The Medicines Company Limited
150 Long Drive, St.  Helters
Auckland, New Zealand

Thomas Lategan
The Medicines Company
One Cambridge Center
Cambridge, Massachusetts 02142

Wendy Gordon
The Medicines Company
One Cambridge Center
Cambridge, Massachusetts 02142

Peyton Marshall
The Medicines Company
One Cambridge Center
Cambridge, Massachusetts 02142

Frederick Oleson
5 Partridge Lane
Concord, Massachusetts 07142

<PAGE>

John Maraganore
49 Constellation Wharf
Charlestown, Massachusetts 02129

H & D Investments 97
60 State Street
Boston, Massachusetts 02109
Attention: Paul P.  Brountas, Esq.

Frederick Oleson
5 Partridge Lane
Concord, Massachusetts 07142

John Maraganore
49 Constellation Wharf
Charlestown, Massachusetts 02129

H & D Investments 97
60 State Street
Boston, Massachusetts 02109
Attention: Paul P.  Brountas, Esq.

<PAGE>

                                   SCHEDULE II

NAME AND ADDRESS OF PURCHASER

E. M. Warburg, Pincus Ventures, L. P.
466 Lexington Avenue
New York, NY 10017

Biotech Growth S.A.
Grafenauweg 4
CH-6301
Zug Switzerland

Hanseatic Americas LDC
450 Park Avenue, Suite 2302
New York, NY 10022

Clive Meanwell
The Medicines Company
One Cambridge Center
Cambridge, MA 02142

Peyton Marshall
The Medicines Company
One Cambridge Center
Cambridge, MA 02142

Jane J. Avinger
207 Avinger Lane
Davidson, NC 28036

H&D Investments 97
Hale and Dorr LLP
60 State Street
Boston, MA 02109

David Ackert
100 Nyala Farm
Westport, CT 06880

Gary S. Roubin Revocable Trust utd
145 East 81st Street
Penthouse B
New York, NY 10028

<PAGE>

                          NAME AND ADDRESS OF PURCHASER

Richard Davis
Tucker Anthony
One Beacon Street
Boston, MA 02108

Charles Schwab and Co., Inc.
FBO: Robert L. Avinger, Jr.
UTA Charles Schwab - 1251-7331
101 South Tyron Street
Charlotte, NC 28280

Bayview Investors, Ltd.
555 California Street, Suite 2600
San Francisco, CA 94104

Morgan Stanley Venture Partners L.P.
1221 Avenue of the Americas, 33rd Fl.
New York, NY 10020

Alta Partners
One Embarcadero Center, Suite 4050
San Francisco, CA 94111

Moore Global Investments, Ltd.
1251 Avenue of the Americas, 53rd Fl.
New York, NY 10020

Remington Investment Strategies, L.P
1251 Avenue of the Americas, 53rd Fl.
New York, NY 10020

Credit Suisse Asset Management
AMPE 3 Utlibergstrasse 231
Postfach 800
Zurich, CH-8070
Switzerland

BancAmerica Robertson Stephens
590 Madison Avenue
New York, NY 10022

<PAGE>

                             AMENDMENT NO. 2 TO THE
               AMENDED AND RESTATED REGISTRATION RIGHTS AGREEMENT
               --------------------------------------------------

This Amendment No. 2 to the Amended and Restated Registration Rights Agreement
dated as of this 19th day of October, 1999 (the "Agreement"), among The
Medicines Company, a Delaware corporation (the "Company"), and the Investors (as
hereinafter defined).

WHEREAS, the Company and the individuals and entities who were signatories
thereto (the "Investors") are parties to the Amended and Restated Registration
Rights Agreement dated as of August 13, 1998, as amended to date (the "Amended
and Restated Registration Rights Agreement"); and

WHEREAS, the Company and certain of the Investors have entered into a Securities
Purchase Agreement of even date herewith with respect to the sale of the Notes
and the Warrants, each as defined therein (the "Securities Purchase Agreement");
and

WHEREAS, the Company and the Investors believe it to be in their mutual best
interests to amend the Amended and Restated Registration Rights Agreement to
provide such Investors with certain rights with respect to the registration
under the Securities Act of 1933, as amended, of the shares of capital stock
issuable upon the conversion of the Notes and/or the exercise of the Warrants;

NOW, THEREFORE, in consideration of the mutual promises and covenants contained
in this Amendment, the parties hereto agree as follows:

1. AMENDMENT TO SECTION 1. Section 1 of the Amended and Restated Registration
Rights Agreement is hereby amended by deleting paragraph (g) of Section 1 in its
entirety and substituting in lieu thereof the following:

         "(g)     the term "Registrable Securities" means (i) any shares of
                  Common Stock issued or issuable on conversion of the Company's
                  Series I Convertible Preferred Stock, Series II Convertible
                  Preferred Stock, Series III Convertible Preferred Stock and
                  Series III-a Convertible Preferred Stock, each $1.00 par value
                  per share (collectively, the "Preferred Stock"), (ii) any
                  additional shares of Common Stock acquired by the Investors,
                  excluding shares acquired by each of Clive A. Meanwell, Peyton
                  Marshall, Wendy Gordon, John Villiger, Thomas Lategan, Helmut
                  Giersiefen, Richard Malcolm and John Nystrom pursuant to the
                  Restricted Stock Purchase Agreements, (iii) any shares of
                  Common Stock issued or issuable upon the exercise of the
                  Common Stock Purchase Warrants issued under the Securities
                  Purchase Agreement dated October 19, 1999 between the Company
                  and the entities and individuals who are signatories thereto,
                  (iv) any shares of Common Stock issued or issuable upon the
                  conversion of the capital stock issued or issuable upon the
                  conversion of the 8% Convertible Notes issued under the
                  Securities Purchase Agreement dated October 19, 1999 between

<PAGE>

                  the Company and the entities and individuals who are
                  signatories thereto, and (v) any capital stock of the Company
                  issued as a dividend or other distribution with respect to, or
                  in exchange for or in replacement of, the shares of Common
                  Stock referred to in clause (i), (ii) ,(iii) or (iv);" and

2. RATIFICATION. In all other respects, the Amended and Restated Registration
Rights Agreement is hereby ratified and confirmed.

3. COUNTERPARTS. This Amendment may be executed in one or more counterparts,
each of which shall be deemed an original and all of which together shall be
considered one and the same agreement.

4. EFFECTIVE DATE. This Amendment shall become effective upon approval by the
Company and the holders of at least 75% of the Registrable Shares (as defined in
the Amended and Restated Registration Rights Agreement).

                                      -2-
<PAGE>

         IN WITNESS WHEREOF, the parties hereto have executed this Amendment No.
2 to the Amended and Restated Registration Rights Agreement as of the date first
above written.

                                  The Medicines Company

                                  By: /s/ Peyton J. Marshall
                                      ---------------------------------------
                                      Name: Peyton J. Marshall
                                      Title: Chief Financial Officer

                                  Holders of at least 75% of the Registrable
                                  Securities

                                  By: /s/ Peyton J. Marshall
                                     -------------------------------
                                      Under Power of Attorney
                                      of Holders attached hereto

                                      -3-

<PAGE>

                             AMENDMENT NO. 3 TO THE
               AMENDED AND RESTATED REGISTRATION RIGHTS AGREEMENT
               --------------------------------------------------

         This Amendment No. 3 to the Amended and Restated Registration Rights
Agreement dated as of this 2nd day of March, 2000 (the "Amendment"), among The
Medicines Company, a Delaware corporation (the "Company"), and the Investors (as
hereinafter defined).

         WHEREAS, the Company and the individuals and entities who were
signatories thereto (the "Investors") are parties to the Amended and Restated
Registration Rights Agreement dated as of August 13, 1998, as amended to date
(the "Amended and Restated Registration Rights Agreement"); and

         WHEREAS, the Company and certain of the Investors have entered into a
Securities Purchase Agreement of even date herewith with respect to the sale of
the Notes and the Warrants, each as defined therein (the "Securities Purchase
Agreement"); and

         WHEREAS, the Company and the Investors believe it to be in their mutual
best interests to amend the Amended and Restated Registration Rights Agreement
to provide such Investors with certain rights with respect to the registration
under the Securities Act of 1933, as amended, of the shares of capital stock
issuable upon the conversion of the Notes and/or the exercise of the Warrants;

         NOW, THEREFORE, in consideration of the mutual promises and covenants
contained in this Amendment, the parties hereto agree as follows:

1. AMENDMENT TO SECTION 1. Section 1 of the Amended and Restated Registration
Rights Agreement is hereby amended by deleting paragraph (g) of Section 1 in its
entirety and substituting in lieu thereof the following:

         "(g)     the term "Registrable Securities" means (i) any shares of
                  Common Stock issued or issuable on conversion of the Company's
                  Series I Convertible Preferred Stock, Series II Convertible
                  Preferred Stock, Series III Convertible Preferred Stock and
                  Series III-a Convertible Preferred Stock, each $1.00 par value
                  per share (collectively, the "Preferred Stock"), (ii) any
                  additional shares of Common Stock acquired by the Investors,
                  excluding shares acquired by each of Clive A. Meanwell, Peyton
                  Marshall, Wendy Gordon, John Villiger, Thomas Lategan, Helmut
                  Giersiefen, Richard Malcolm and John Nystrom pursuant to the
                  Restricted Stock Purchase Agreements, (iii) any shares of
                  Common Stock issued or issuable upon the exercise of the
                  Common Stock Purchase Warrants issued under the Securities
                  Purchase Agreement dated October 19, 1999 between the Company
                  and the entities and individuals who are signatories thereto,
                  (iv) any shares of Common Stock issued or issuable upon the
                  conversion of the capital stock issued or issuable upon the
                  conversion of the 8% Convertible Notes issued under the
                  Securities Purchase Agreement

<PAGE>

                  dated October 19, 1999 between the Company and the entities
                  and individuals who are signatories thereto, (v) any shares of
                  Common Stock issued or issuable upon the exercise of the
                  Common Stock Purchase Warrants issued under the Securities
                  Purchase Agreement dated March 2, 2000 between the Company and
                  the entities and individuals who are signatories thereto, (vi)
                  any shares of Common Stock issued or issuable upon the
                  conversion of the capital stock issued or issuable upon the
                  conversion of the 8% Convertible Notes issued under the
                  Securities Purchase Agreement dated March 2, 2000 between the
                  Company and the entities and individuals who are signatories
                  thereto, and (vii) any capital stock of the Company issued as
                  a dividend or other distribution with respect to, or in
                  exchange for or in replacement of, the shares of Common Stock
                  referred to in clause (i), (ii) ,(iii), (iv), (v) or (vi);"
                  and

2. RATIFICATION. In all other respects, the Amended and Restated Registration
Rights Agreement is hereby ratified and confirmed.

3. COUNTERPARTS. This Amendment may be executed in one or more counterparts,
each of which shall be deemed an original and all of which together shall be
considered one and the same agreement.

4. EFFECTIVE DATE. This Amendment shall become effective upon approval by the
Company and the holders of at least 75% of the Registrable Shares (as defined in
the Amended and Restated Registration Rights Agreement).

                  [Remainder of page intentionally left blank]

                                      -2-

<PAGE>

         IN WITNESS WHEREOF, the parties hereto have executed this Amendment No.
3 to the Amended and Restated Registration Rights Agreement as of the date first
above written.

                                  The Medicines Company

                                  By: /s/ Peyton J. Marshall
                                     ---------------------------------------
                                  Name: Peyton J. Marshall
                                  Title: Chief Financial Officer

                                  Holders of at least 75% of the Registrable
                                  Securities

                                  By: /s/ Peyton J. Marshall
                                     ---------------------------------------
                                      Under Power of Attorney
                                      of Holders attached hereto

                                      -3-

<PAGE>

                             AMENDMENT NO. 4 TO THE
               AMENDED AND RESTATED REGISTRATION RIGHTS AGREEMENT
               --------------------------------------------------

         This Amendment No. 4 to the Amended and Restated Registration Rights
Agreement dated as of this 17 day of May, 2000 (the "Amendment"), among The
Medicines Company, a Delaware corporation (the "Company"), and the Investors (as
hereinafter defined).

         WHEREAS, the Company and the individuals and entities who were
signatories thereto (the "Investors") are parties to the Amended and Restated
Registration Rights Agreement dated as of August 12, 1998, as amended to date
(the "Amended and Restated Registration Rights Agreement"); and

         WHEREAS, the Company and certain of the Investors have entered into a
Series IV Convertible Preferred Stock Purchase Agreement of even date herewith
with respect to the sale of the Preferred Shares, each as defined therein (the
"Purchase Agreement"); and

         WHEREAS, the Company and the Investors believe it to be in their mutual
best interests to amend the Amended and Restated Registration Rights Agreement
to provide such Investors with certain rights with respect to the registration
under the Securities Act of 1933, as amended, of the shares of capital stock
issuable upon the conversion of the Preferred Shares;

         NOW, THEREFORE, in consideration of the mutual promises and covenants
contained in this Amendment, the parties hereto agree as follows:

1. AMENDMENT TO SECTION 1. Section 1 of the Amended and Restated Registration
Rights Agreement is hereby amended by deleting paragraph (g) of Section 1 in its
entirety and substituting in lieu thereof the following:

         "(g) the term "Registrable Securities" means (i) any shares of Common
         Stock issued or issuable on conversion of the Company's Series I
         Convertible Preferred Stock, Series II Convertible Preferred Stock,
         Series III Convertible Preferred Stock and Series IV Convertible
         Preferred Stock, each $1.00 par value per share (collectively, the
         "Preferred Stock"), (ii) any additional shares of Common Stock acquired
         by the Investors [prior to the Initial Public Offering], excluding
         shares acquired by each of Clive A. Meanwell, Peyton Marshall, Wendy
         Gordon, John Villiger, Thomas Lategan, Helmut Giersiefen, Richard
         Malcolm and John Nystrom pursuant to the Restricted Stock Purchase
         Agreements[, and any other shares acquired by an Investor pursuant to
         the Company's 1998 Stock Incentive Plan], (iii) any shares of Common
         Stock issued or issuable upon the exercise of the Common Stock Purchase
         Warrants issued under the Securities Purchase Agreement dated October
         19, 1999 between the Company and the entities and individuals who are
         signatories thereto, (iv) any shares of Common Stock issued or issuable
         upon the exercise of the Common Stock Purchase Warrants issued under
         the Securities Purchase Agreement dated March 2, 2000 between the
         Company and the entities and individuals who are signatories thereto,
         and (v) any capital stock of the Company issued as a

<PAGE>

         dividend or other distribution with respect to, or in exchange for or
         in replacement of, the shares of Common Stock referred to in clause
         (i), (ii), (iii) or (iv);" and

2. RATIFICATION. In all other respects, the Amended and Restated Registration
Rights Agreement is hereby ratified and confirmed.

3. COUNTERPARTS. This Amendment may be executed in one or more counterparts,
each of which shall be deemed an original and all of which together shall be
considered one and the same agreement.

4. EFFECTIVE DATE. This Amendment shall become effective upon approval by the
Company and the holders of at least 75% of the Registrable Shares (as defined in
the Amended and Restated Registration Rights Agreement).

                  [Remainder of page intentionally left blank]

                                      -2-

<PAGE>

         IN WITNESS WHEREOF, the parties hereto have executed this Amendment No.
4 to the Amended and Restated Registration Rights Agreement as of the date first
above written.

                                  The Medicines Company

                                  By: /s/ Peyton J. Marshall
                                     ---------------------------------------
                                      Name: Peyton J. Marshall
                                      Title: Chief Financial Officer

                                  Holders of at least 75% of the Registrable
                                  Securities

                                  By: /s/ Peyton J. Marshall
                                     ---------------------------------------
                                      Under Power of Attorney
                                      of Holders attached hereto

                                      -3-

<PAGE>
      Amendment to the Amended and Restated Registration Rights Agreement

                                 June 19, 2002

     A second sentence in Section 11 of the Amended and Restated Registration
Rights Agreement dated as of August 12, 1998, as amended, by and between The
Medicines Company and the parties thereto (the "Agreement") shall be inserted
so that Section 11 of the Agreement, as amended, shall read in its entirety as
follows:

          "The registration rights set forth in this Agreement shall not be
          available to any Holder if, in the written opinion of regular, outside
          counsel to the Company, all of the Registrable Securities then owned
          by such Holder could be sold in any ninety (90) day period pursuant to
          Rule 144 under the Securities Act (without giving effect to the
          provisions of Rule 144(k)). Upon such event, the Registrable
          Securities held by such Holder shall cease to be Registrable
          Securities for purposes of this Agreement."

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