<PAGE>

                   AMENDED AND RESTATED CONTRIBUTION AGREEMENT

     This Amended and Restated Contribution Agreement (the "AGREEMENT") is made
and entered into as of November __, 1997, by and among Stephen Friend
("FRIEND"), Leroy Hood ("HOOD") and the Fred Hutchinson Cancer Research Center
(the "FHCRC") (Friend, Hood and the FHCRC are individually referred to as a
"CONTRIBUTOR" and collectively referred to the "CONTRIBUTORS"), and Rosetta
Inpharmatics, Inc., a Delaware corporation (the "Company").

                                    RECITALS

     A.   The Company and the Contributors desire to amend and restate in its
entirety the Contribution Agreement entered into as of June 6, 1997 (the
"ORIGINAL AGREEMENT") in order to clarify certain provisions of the Original
Agreement.

     B.   Friend is the record owner of 696,200 shares of Common Stock of the
Company and desires to transfer up to 92,186 shares of such Common Stock (the
"FRIEND STOCK") to the Company pursuant to the terms and conditions of this
Agreement.

     C.   Hood is the record owner of 531,000 shares of Common Stock of the
Company and desires to transfer up to 70,312 shares of such Common Stock (the
"HOOD STOCK") to the Company pursuant to the terms and conditions of this
Agreement.

     D.   The FHCRC is the record owner of 283,200 shares of Common Stock of the
Company and desires to transfer up to 37,500 shares of such Common Stock (the
"FHCRC STOCK") (the Friend Stock, Hood Stock and FHCRC Stock are collectively
referred to as the "CONTRIBUTION STOCK") to the Company pursuant to the terms
and conditions of this Agreement.

     E.   The Company issued a warrant to Olympic Venture Partners dated June 6,
1997 for the purchase of an aggregate of 250,000 shares of Common Stock at a
purchase price of $0.05 per share (the "WARRANT").

     F.   The Contributors desire to contribute all or a portion of the
Contribution Stock to the Company on the terms and conditions set forth in this
Agreement in the event the Warrant is exercised for more than an aggregate of
50,000 shares of Common Stock.

                                    AGREEMENT

     The parties hereby agree as follows:

     1.   TRANSFER AND SALE. Subject to the terms and conditions of this
Agreement, in the event the Warrant is exercised for more than an aggregate of
50,000 shares of Common Stock, each Contributor agrees to transfer and
contribute to the capital stock of the Company his or its Pro Rata Portion (as
defined below) of the Contribution Stock, and the Company agrees to accept such
shares from each Contributor as a capital contribution.


<PAGE>

     2.   PRO RATA PORTION. Each Contributor's pro rata portion of the
Contribution Stock equals the amount by which the number of shares of Common
Stock for which the Warrant is exercised exceeds 50,000, multiplied by a
fraction the numerator of which is the respective amount of Common Stock owned
by such Contributor and the denominator of which is 1,510,400 (the "PRO RATA
PORTION"). By way of example, but not of limitation, if the Warrant is exercised
for 150,000 shares, Friend's Pro Rata Portion would be 46,094, Hood's Pro Rata
Portion would be 35,156 and the FHCRC's Pro Rata Portion would be 18,750.

     3.   RECAPITALIZATIONS. In the event the Company effects a
recapitalization, either through a stock-split, dividend payable in shares of
capital stock of the Company, reclassification, exchange or otherwise, then the
formula used to calculate each Contributor's Pro Rata Portion shall be adjusted
as appropriate to fully reflect such recapitalization and to carry out the
intent and purpose of this Agreement.

     4    LEGENDS. Each Contributor authorizes the Company and its agents to
place on each certificate for shares which the Company may acquire pursuant to
this Agreement the following legend stating that such stock is subject to this
Agreement (in addition to any other legends that may be required):

             "THE SHARES REPRESENTED BY THIS CERTIFICATE ARE SUBJECT TO AN
        AMENDED AND RESTATED CONTRIBUTION AGREEMENT DATED AS OF NOVEMBER
        __, 1997 (A COPY OF WHICH MAY BE OBTAINED UPON WRITTEN REQUEST
        FROM THE CORPORATION) AND BY ACCEPTING ANY INTEREST IN SUCH
        SHARES THE PERSON ACCEPTING SUCH INTEREST SHALL BE DEEMED TO
        AGREE AND SHALL BECOME BOUND BY ALL THE PROVISIONS OF SAID
        CONTRIBUTION AGREEMENT."

     5    SPECIFIC ENFORCEMENT. Each Contributor expressly agrees that the
Company will be irreparably damaged if this Agreement is not specifically
enforced. Upon a breach or threatened breach of the terms, covenants and/or
conditions of this Agreement by any Contributor, in addition to all other
remedies available at law or in equity, the Company shall be entitled to a
temporary or permanent injunction, without showing any actual damage, and/or a
decree for specific performance, in accordance with the provisions of this
Agreement.

     6    MISCELLANEOUS.

          (a)  GOVERNING LAW. This Agreement and all acts and transactions
pursuant hereto and the rights and obligations of the parties hereto shall be
governed, construed and interpreted in accordance with the laws of the State of
Washington, without giving effect to principles of conflicts of law.

          (b)  ENTIRE AGREEMENT; ENFORCEMENT OF RIGHTS. Except as expressly set
forth herein, this Agreement sets forth the entire agreement and understanding
of the parties relating to the subject matter herein and merges all prior
discussions between them. No

                                      -2-
<PAGE>

modification of or amendment to this Agreement, nor any waiver of any rights
under this Agreement, shall be effective unless in writing signed by the parties
to this Agreement. The failure by either party to enforce any rights under this
Agreement shall not be construed as a waiver of any rights of such party.

          (c)  SEVERABILITY. If one or more provisions of this Agreement are
held to be unenforceable under applicable law, the parties agree to renegotiate
such provision in good faith. In the event that the parties cannot reach a
mutually agreeable and enforceable replacement for such provision, then (i) such
provision shall be excluded from this Agreement, (ii) the balance of the
Agreement shall be interpreted as if such provision were so excluded and (iii)
the balance of the Agreement shall be enforceable in accordance with its terms.

          (d)  CONSTRUCTION. This Agreement is the result of negotiations
between and has been reviewed by each of the parties hereto and their respective
counsel, if any; accordingly, this Agreement shall be deemed to be the product
of all of the parties hereto, and no ambiguity shall be construed in favor of or
against any one of the parties hereto.

          (e)  NOTICES. Any notice required or permitted by this Agreement shall
be in writing and shall be deemed sufficient when delivered personally or sent
by telegram or fax or forty-eight (48) hours after being deposited in the U.S.
mail, as certified or registered mail, with postage prepaid, and addressed to
the party to be notified at such party's address as set forth below or as
subsequently modified by written notice.

          (f)  COUNTERPARTS. This Agreement may be executed in two or more
counterparts, each of which shall be deemed an original and all of which
together shall constitute one instrument.

          (g)  SUCCESSORS AND ASSIGNS; TRANSFER OF STOCK. The rights and
obligations of the Contributors under this Agreement may only be assigned with
the prior written consent of the Company. Each Contributor understands that the
Company is entitled to withhold its consent to transfer of the Stock or
assignment of such Contributor's rights and obligations under this Agreement
unless such Contributor requires as a condition to any such transfer or
assignment that the Contributor's transferee or assignee execute an agreement
similar to this Agreement or otherwise agree to be bound by terms and conditions
similar to those contained in this Agreement.

                            [Signature Page Follows]


                                      -3-
<PAGE>

     The parties have executed this Agreement as of the date first set forth
above.

                                  THE COMPANY:

                                  ROSETTA INPHARMATICS, INC.

                                  By:
                                     ------------------------------------------

                                  Title:
                                        ---------------------------------------


                                  THE CONTRIBUTORS:

                                  ---------------------------------------------
                                  Stephen H. Friend

                                  ---------------------------------------------
                                  Leroy E. Hood

                                  THE FRED HUTCHINSON CANCER
                                    RESEARCH CENTER

                                  By:
                                     ------------------------------------------

                                  Title:
                                        ---------------------------------------


                                      -4-
<PAGE>

                             CONTRIBUTION AGREEMENT

                                CONSENT OF SPOUSE

     I, ___________________, spouse of _______________, have read and approve
the foregoing Amended and Restated Contribution Agreement (the "AGREEMENT"). In
consideration of the terms and conditions as set forth in the Agreement, I
hereby appoint my spouse as my attorney-in-fact with respect to the exercise of
any rights and obligations under the Agreement and agree to be bound by the
provisions of the Agreement insofar as I may have any rights or obligations in
the Agreement or any shares subject thereto under the community property laws of
the State of Washington or similar laws relating to marital property in effect
in the state of our residence as of the date of the Agreement.

Dated:  November ___, 1997

                                        ------------------------------
                                        (Signature)

                                        ------------------------------
                                        (Printed name)


                                      -5-