To investigate the paradoxical actions of human chorionic gonadotropin (hCG) on ovarian function, 1000 IU of hCG were administered to monkeys during the late follicular phase of 16 menstrual cycles, either on day 9 or day 11 after the onset of menses. Retrospectively, hormone profiles indicated that 6 of 16 hCG treatments were given coincidentally with incipient gonadotropin surges. In the remaining 10 cycles, hCG was given prior to the initiation of spontaneous gonadotropin surges. No untoward effects of hCG were observed in monkeys treated coincidentally with, or after, the onset of spontaneous surges of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). In the 10 cycles in which hCG was injected prior to initiation of endogenous gonadotropin surges, induced atresia of the expected dominant follicle was presumed from the absence of the anticipated midcycle elevations of serum 17β-estradiol, LH, and FSH, and lack of a luteal phase increase in progesterone concentration. Resumption of cyclic ovarian function was delayed significantly (P 3 weeks). Among these 5 monkeys, the concentrations of LH, estradiol, and progesterone were indistinguishable from those of the remaining 5, in which serum FSH concentrations did not change appreciably. The data indicate that, after the initiation of the preovulatory gonadotropin surges, the ovaries were not susceptible to these pharmacologic impairments induced by hCG. In contrast, when administered prior to initiation of the spontaneous FSH and LH surges, hCG induced (1) apparent atresia of the dominant follicle; (2) arrest of cyclic ovarian function lasting more than 3 weeks; and (3) in 5 of 10 monkeys, an altered modulation of tonic FSH secretion, independent of LH release, where serum FSH persisted at levels about 3-fold above normal.