<PAGE>


                               AMENDMENT NO. 1 TO

                     GENE EXPRESSION COLLABORATION AGREEMENT

         This Amendment No. 1 (this "AMENDMENT") entered into as of May 25, 2000
amends the Gene Expression Collaboration Agreement dated October 1, 1999 (the
"AGREEMENT"), by and between Rosetta Inpharmatics, Inc., a corporation organized
under the laws of the State of Delaware ("ROSETTA"), and Agilent Technologies,
Inc., a corporation organized under the laws of the State of Delaware and
formerly a division of Hewlett-Packard Company ("AGILENT").

                                    RECITALS

         A. Rosetta and Agilent entered into the Agreement pursuant to which
Rosetta and Agilent agreed to collaborate to design, develop, manufacture,
commercialize and use Collaborative Products (as defined in the Agreement).

         B. Rosetta and Agilent now agree to amend the Agreement in certain
respects as hereinafter provided.

         C. Rosetta and Agilent agree that all other terms and conditions of the
Agreement remain in full force and effect.

         In consideration of the mutual promises contained herein, the parties
hereto agree as follows:

                                    AMENDMENT

1. TERMS. Capitalized terms in this Amendment shall have the same meaning as
those in the Agreement, unless specifically defined in this Amendment. All
section and paragraph references refer to sections or paragraphs, as applicable,
in the Agreement. References to the term "Agreement" in the Agreement shall be
deemed to include this Amendment.

2. INTERPRETATION. Except as expressly modified herein, the Agreement shall
remain in full force and effect in accordance with its terms. To the extent
there are any inconsistencies or ambiguities between this Amendment and the
Agreement, the terms of this Amendment shall supersede the Agreement.

3. AMENDMENTS.

         a. The fourth and fifth sentences of Section 2.4(b) are hereby amended
and restated in their entirety as follows:

                  "Agilent and Rosetta hereby agree to Agilent's licensing of
the Rosetta Proposed Enhancements pursuant to the terms set forth in Section
2.6(a)(iv). In consideration therefor, Agilent shall pay to Rosetta, in
accordance with Section 7.7 hereof, a royalty equal to [* * * ] of the Net
Revenues associated with the Royalty Bearing Portion of the Pamela System."


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* MATERIAL HAS BEEN OMITTED PURSANT TO A REQUEST FOR CONFIDENTIAL TREATMENT,
    AND SUCH MATERIAL HAS BEEN FILED SEPARATELY WITH THE SEC.
<PAGE>

         b. The first sentence of Section 7.6 is hereby amended and restated in
its entirety as follows:

                  "Agilent will, subject to the next following sentence,
         establish prices for Collaboration Products offered by Agilent that
         reflect in good faith the fair market value of each such Collaboration
         Product, PROVIDED, HOWEVER, Agilent shall not offer to any customer a
         discount in excess of [* * * ] off of the Resolver list price without
         the prior written approval of Rosetta."

         c. Section 7.7 is hereby amended and restated in its entirety as
follows:

                  "7.7 PAYMENTS AND REPORTS. Agilent shall make written reports
(consistent with GAAP or such other policies and practices as required by the
AFM) and royalty and revenue sharing payments (including payment of all amounts
related to the sale or other disposition in TAP Sales or Commercial Sales of the
Resolver Platform and maintenance and support contracts for the Resolver
Platform as provided in Section 7.4(a) hereof) to Rosetta within thirty (30)
days after the close of each Agilent fiscal quarter during the Term regardless
of whether Agilent shall at such time under the AFM, GAAP or otherwise be able
to book the entire amount of any such royalty or revenue sharing payment as
income for such quarter, and regardless of any extended payment terms granted by
Agilent in connection with the sale or other disposition of Collaboration
Products. Such reports shall show for such fiscal quarter sales by Agilent, its
Affiliates and sublicensees, if any, of Collaboration Products, details of the
quantities of each Collaboration Product sold (including type and quantity of
each category of Array), Net Revenues from sales of Collaboration Products on a
product-by-product basis, trade discounts allowed and taken, and the revenue
sharing and royalty amounts due to Rosetta thereon pursuant hereto. In the event
Agilent shall be required under the AFM or GAAP to write off amounts owed, or
refund amounts previously paid, to it as a result of performance issues related
to Resolver, Agilent may during the period wherein Resolver Net Revenues are
less than [* * *] deduct Rosetta's proportionate share of such amounts from
payments required to be made to Rosetta pursuant to the first sentence of this
Section 7.7, PROVIDED, HOWEVER, the report accompanying such payment shall
describe in reasonable detail the reasons for such deduction and the customer to
which such deduction relates. In the event Rosetta shall have sold any
Collaboration Product or received any revenue in connection with a sale of a
Collaboration Product (other than pursuant to the immediately preceding
sentence), Rosetta shall likewise deliver to Agilent a written report
(consistent with GAAP) within thirty days (30) days after the close of each
Rosetta fiscal quarter during which any such Collaboration Product was sold or
revenue received by Rosetta and pay over to Agilent, concurrent with the
delivery of such report, any amounts received by Rosetta in connection with such
sale or which were otherwise received, net of the royalty or revenue sharing
amounts otherwise due Rosetta in connection therewith."

         d. Section 7.10 is hereby amended to add the following sections:

            (f)  In the event Agilent shall use Oligo Set Design Services
                 provided by Rosetta for whatever purpose, Agilent shall, upon
                 receipt of an invoice related thereto, reimburse Rosetta in an
                 amount to be agreed prior to Rosetta's provision of such
                 services, PROVIDED, HOWEVER, such amount shall

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* MATERIAL HAS BEEN OMITTED PURSANT TO A REQUEST FOR CONFIDENTIAL TREATMENT,
    AND SUCH MATERIAL HAS BEEN FILED SEPARATELY WITH THE SEC.
<PAGE>

                  in no event be less than the fully-burdened costs incurred by
                  Rosetta in connection with the provision of such services.

            (g)   In recognition of the revenue sharing and royalties specified
                  in Exhibit L, Agilent and Rosetta affirm that, for the purpose
                  of designing Arrays under this Agreement, Rosetta's Oligo Set
                  Design Technology will be completely accessible and shared
                  with Agilent and that Agilent's Pamela-Resident Set Design
                  Technology will be completely accessible and shared with
                  Rosetta.

            (h)   Rosetta hereby acknowledges that it has reviewed the Supply
                  Agreement and License between Agilent and OGT, dated as of the
                  6th of December, 1999, particularly those provisions relating
                  to the supply of In Situ Arrays to OGT by Agilent and the
                  licenses to Rosetta patents providing for the use of such
                  Arrayers. Rosetta hereby acknowledges and consents to the
                  terms of such license, and the Agreement is hereby amended to
                  reflect such acknowledgement and consent.

         e. Section 13.8 is hereby amended and restated in its entirety as
follows:

            "13.8 NOTICE. Any notice or other communication required or
permitted to be given to either Party hereto shall be in writing and shall be
deemed to have been properly given and to be effective on the date of delivery
if delivered in person, by facsimile or by nationally recognized express
courier, or effective fourteen (14) days after mailing by U.S. Postal Service,
postage prepaid, as Registered or Express Mail, postage paid, to the other Party
at the following address:

                  Rosetta:          Rosetta Inpharmatics, Inc.
                                    12040 - 115th Ave. NE
                                    Kirkland, WA  98034
                                    Attn.:  President

                                    with copy to:
                                    Venture Law Group
                                    4750 Carillon Point
                                    Kirkland, WA  98033
                                    Attn.:  Mark Handfelt

                  Agilent:          Agilent Technologies, Inc.
                                    3500 Deer Creek Road
                                    Palo Alto, CA  94304
                                    Attn.: General Manager, Bioscience Products

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* MATERIAL HAS BEEN OMITTED PURSANT TO A REQUEST FOR CONFIDENTIAL TREATMENT,
    AND SUCH MATERIAL HAS BEEN FILED SEPARATELY WITH THE SEC.

<PAGE>


                                    with copy to:
                                    Agilent Technologies, Inc.
                                    Agilent Legal Dept.
                                    3000 Hanover Street
                                    Palo Alto, CA  94304
                                    Attn.:  General Counsel


         f. EXHIBIT L is hereby amended and restated in its entirety as the
attached EXHIBIT L.

                            [Signature page follows]







                                      -4-

* MATERIAL HAS BEEN OMITTED PURSANT TO A REQUEST FOR CONFIDENTIAL TREATMENT,
    AND SUCH MATERIAL HAS BEEN FILED SEPARATELY WITH THE SEC.

<PAGE>


         IN WITNESS WHEREOF, the Parties have executed this Amendment as of the
date first set forth above.

ROSETTA INPHARMATICS, INC.                  AGILENT TECHNOLOGIES, INC.

By: _________________________________       By: _______________________________

Name: _______________________________       Name:______________________________

Title: ______________________________       Title:_____________________________









                      SIGNATURE PAGE TO AMENDMENT NO. 1 TO
                     GENE EXPRESSION COLLABORATION AGREEMENT

*Confidential treatment is requested for the language that has been underscored
or marked. Such language has been deleted from the copy filed with the SEC.


* MATERIAL HAS BEEN OMITTED PURSANT TO A REQUEST FOR CONFIDENTIAL TREATMENT,
    AND SUCH MATERIAL HAS BEEN FILED SEPARATELY WITH THE SEC.

<PAGE>

                                    EXHIBIT L
                     ROYALTY-BEARING COLLABORATION PRODUCTS


<TABLE>
<CAPTION>

-------------------------------------------------- ------------------------------------------ ---------------
PRODUCT                                            % ROYALTY RATE PAID ROSETTA BY AGILENT     STACKING
-------------------------------------------------- ------------------------------------------ ---------------
<S>                                                <C>                                        <C>
[* * *]                                            [* * *]                                    [* * *]
-------------------------------------------------- ------------------------------------------ ---------------
[* * *]                                            [* * *]                                    [* * *]
-------------------------------------------------- ------------------------------------------ ---------------
</TABLE>

<TABLE>
<CAPTION>

Revenue-Sharing Collaboration Products
-------------------------------------------- -------------------------------- -------------------------------
REVENUE SOURCE                               REVENUE SHARE % DUE AGILENT      REVENUE SHARE % DUE ROSETTA
-------------------------------------------- -------------------------------- -------------------------------
<S>                                          <C>                              <C>
[* * *]                                      [* * *]                          [* * *]
-------------------------------------------- -------------------------------- -------------------------------
[* * *]                                      [* * *]                          [* * *]
-------------------------------------------- -------------------------------- -------------------------------
[* * *]                                      [* * *]                          [* * *]
-------------------------------------------- -------------------------------- -------------------------------
[* * *]                                      [* * *]                          [* * *]
-------------------------------------------- -------------------------------- -------------------------------
</TABLE>


<TABLE>
<CAPTION>

Collaboration Products
Subject to Neither Royalty nor Revenue Sharing
----------------------------------------------------- ------------------------------- -----------------------
Product                                               Royalty/Revenue Share           Royalty Stacking
----------------------------------------------------- ------------------------------- -----------------------
<S>                                                   <C>                             <C>
[* * *]                                               [* * *]                         [* * *]
----------------------------------------------------- ------------------------------- -----------------------
[* * *]                                               [* * *]                         [* * *]
----------------------------------------------------- ------------------------------- -----------------------
</TABLE>



*Confidential treatment is requested for the language that has been underscored
or marked. Such language has been deleted from the copy filed with the SEC.



* MATERIAL HAS BEEN OMITTED PURSANT TO A REQUEST FOR CONFIDENTIAL TREATMENT,
    AND SUCH MATERIAL HAS BEEN FILED SEPARATELY WITH THE SEC.