The nonsteroidal antiinflammatory agents diclofenac, fenoprofen and aspirin were tested to determine how well they inhibit the preovulatory elevation in prostaglandin (PG) production in rabbit follicles in comparison to indomethacin. In addition, the steroidal antiinflammatory agent dexamethasone and the antipyretic agent acetaminophen were tested. The agents were administered 8 h after the ovulatory process was stimulated by hCG (50 I.U./kg). At 10 h after hCG (i.e., at the expected time of ovulation) control follicles had PGF and PGE levels of 370.0 and 582.6 pg/mg of follicle, respectively. Diclofenac inhibited PG production the most--reducing PGF and PGE to 22.8 and 53.6 pg/mg, respectively. Indomethacin reduced the PGF and PGE levels to 27.4 and 76.6 pg/mg, respectively. Fenoprofen was less effective, reducing the PGF and PGE to 77.8 and 222.4 pg/mg, respectively. Aspirin reduced the PGF and PGE to 123.4 and 174.6 pg/mg, respectively. Dexamethasone and acetaminophen did not inhibit PG production. Ovulation was completely inhibited by diclofenac and indomethacin, partially inhibited by fenoprofen, and unaffected by aspirin, acetaminophen, or dexamethasone. The results suggest that any potent nonsteroidal antiinflammatory agent can inhibit ovulation provided it adequately reduces PG production; whereas steroidal antiinflammatory agents are ineffective. The antiinflammatory agent must completely abolish the preovulatory elevation in PGs in mature follicles in order to totally inhibit ovulation.