The effects of cortisol acetate were studied on immature gonadotrophin treated rats, mature intact and hysterectomized cycling females, gestating and pseudopregnant subjects with pituitary implants, and mature males. Observations included growth, organ morphology, histological, follicular and corpora lutea counts and measurements, vaginal smears and ovarian progesterone assays. The diameters of larger follicles were potentiated and the incidence of follicles exhibiting histological atresia increased. Luteinization occurred more rapidly but many corpora lutea were cystic in treated immature rats. The cycles of mature rats exhibited dose-related prolongation of the dioestrous period which was unaffected by hysterectomy. Ovulation, conception, and nidation were unchanged by chronic treatment, but embryonic mortality was increased. The combined uterine-decidual tissue weight was inhibited to a greater extent than the various conceptus elements. Uterine growth was unaffected in pseudopregnant immature and mature rats, but under conditions of oestrogen predomination inhibition was marked. Ovarian progesterone concentration was reduced by treatment only in pregnant rats, and the significance of this finding is discussed. No evidence of alterations in the endogenous gonadotrophic secretions was found in any of these experiments. It is concluded that the administration of excess cortisol acetate exerted no true inhibitory influences on gonadal activity, unlike the potent inhibitory effects of adrenocorticotrophin.