Three phosphodiesterase (PDE) type III inhibitors were tested and found to inhibit Xenopus oocyte maturation induced by insulin with apparent IC₅₀ values of 2.2 ± 0.2 μM CI-930, 25 ± 3 μM imazodan (CI-914), and 786 ± 237 μM piroximone (MDL 19,205). The same rank order of potencies was observed for inhibition of insulin-like growth factor-l (IGF-l)-induced oocyte maturation, with IC₅₀ values of 5.5 ± 0.9 μM CI-930, 54 ± 4 μM imazodan, and 1190 ± 395 μM piroximone. Oocyte maturation induced by microinjection of Ha p21 ras was also inhibited by pretreatment of oocytes with CI-930 or imazodan, with IC₅₀ values of 4.3 ± 1.2 and 59 ± 4 μM, respectively. Progesterone-induced maturation was not affected by PDE III inhibitor action; and, neither type IV PDE inhibitors (Ro 20,1724 or rolipram) nor dipyridamole (a type V PDE inhibitor) inhibited cell division induced by IGF-I or microinjected Ha p21ras. In addition, while insulin-stimulated oocyte PDE activity measured in vivo after microinjection of 200 MM [3H] cAMP was inhibited by nonselective and type IIIspecific drugs (with IC₅₀ values of 4.2 ± 1.8 μM CI- 930 and 26 ± 6 μM imazodan), type IV and type V inhibitors did not inhibit hormone-stimulated enzyme activity. This pharmacological evidence demonstrates a necessary role for PDE III in insulin-, IGF-I-, and p21ras-induced meiotic cell division in Xenopus laevis oocytes.