In order to demonstrate the possible role of prostaglandins in preovulatory follicular development, immature mice superovulated with pregnant mare serum followed 40 hours later by luteinizing hormone (LH) were treated with the prostaglandin-synthetase inhibitor, indomethacin. Indomethacin (10 mg/kg) injected at varying intervals prior to or following LH inhibited ovulation most effectively when administered within 2 hours of the ovulatory gonadotropin. This inhibition was accompanied by (1) suppression of the morphological changes normally occurring within the follicular wall during preovulatory development and (2) failure of germinal vesicle breakdown (GVBD) in two-thirds of the follicles examined. When GVBD occurred, indomethacin treatment appeared to delay meiotic maturation. Cumulus tissue was more compact than in control follicles and maintained a close association with the oocyte. These results suggest that alterations in the morphology of the follicle prior to ovulation--specifically, thinning of the apical follicular wall and meiotic maturation--are regulated by prostaglandins.