Amendment to the Collaborative Research Agreement

         This  Agreement  (the "2000  Amendment") is entered into as of March 1,
2000 by and between Pfizer Inc. ("Pfizer"),  a Delaware  corporation,  having an
office at 235 East 42nd Street,  New York, New York 10017 and its Affiliates and
Microcide Pharmaceuticals,  Inc. ("Microcide"), a California corporation, having
an office at 850 Maude Avenue, Mountain View, California 94043.

         Whereas,  the parties  have  previously  entered  into a  Collaborative
Research Agreement (the "1996 Research Agreement") dated as of March 1, 1996 and
amended as of May 6, 1998,  (the "1998  Amendment")  and a License  and  Royalty
Agreement (the "1996 License Agreement") dated as of March 1, 1996.

Now Therefore,  in consideration of the mutual convenants and promises set forth
in the 1996  Research  Agreement  and the 1998  Amendment,  the parties agree as
follows:

1)       The following sentence s]hall be added to the end of Section 2.2 of the
         1996 Research Agreement:

"The Annual Research Plan for Commitment Year 5, shall be appended to and made a
part of the Agreement as Exhibit C and shall be effective as of March 1, 2000."

2)       Section  3.2 of the  1996  Research  Agreement  shall  be  deleted  and
         replaced by the following:

         Commitment Year                             Annual Commitment

               1                                          $4.2MM
               2                                          $4.2MM
               3                                          $4.2MM
               4                                          $4.2MM
               5                                          $2.1MM

3)       Section  3.3 of the  1996  Research  Agreement  shall  be  deleted  and
         replaced by the following:


"Payments  by Pfizer to cover  Microcide's  total,  full-time  employees  (FTEs)
devoted to the Research Program [*]. Such payments shall be used by Microcide to
perform the Research  Program.  Microcide shall dedicate at least [*] ([*]) FTEs
to perform the  Research  Program and conduct the Annual  Research  Program Plan
during [*]."


Certain  information on this page has been omitted and filed separately with the
Commission.  Confidential  treatment  has been  requested  with  respect  to the
omitted portions.



[*] Confidential Treatment Requested

<PAGE>


All other terms and  conditions  of 1996  Research  Agreement,  the 1996 License
Agreement and 1998 Amendment shall remain the same and in full force and effect.

Please indicate  agreement by signing below.  Return an executed original to Dr.
Edward D. Pagani at Pfizer Central Research.

Agreed:  Microcide Pharmaceuticals, Inc.  Agreed:  Pfizer Inc.

By:  /s/ James E. Rurka                   By:  /s/  George M. Milne, Jr.
     ----------------------------------        --------------------------------
         Mr. James E. Rurka                         Dr. George M. Milne, Jr.
         President and CEO                          President, Pfizer Central
                                                    Research

Date:    March 6, 2000                    Date:     March 1, 2000



<PAGE>


                                                 MICROCIDE PHARMACEUTICALS, INC.
                                                                    CONFIDENTIAL



                                    Exhibit C

                                       [*]



[*] Confidential Treatment Requested



<PAGE>





                                   Addendum A

                                      [*]





[*] Confidential Treatment Requested


<PAGE>

Pfizer-Microcide                                                      01/07/2000
Confidential

                                      [*]


                                   Addendum B



[*] Confidential Treatment Requested