Cyclophosphamide (CTX) is a potent ovarian toxicant. Previous studies of the acute effects of CTX in the rat have demonstrated widespread ovarian follicle atresia, reduced serum estradiol, and progesterone with normal serum LH and FSH. The present investigations demonstrate that a single injection of CTX induces ovarian toxicity that reflects the loss of growing ovarian follicles. CTX induces a sensitization of serum FSH in response to GnRH within 24 h; this sensitization is lost by 7 days, and after 14 days the animals are capable of normal mating behavior. The observed protection of primordial follicles from the acute administration of CTX under these experimental circumstances may be related to the stage of the granulosa cell cycle of these follicles.