Gonadectomy resulted in a gradual increase in plasma gonadotropin levels in female mice. At certain intervals after ovariectomy, a single administration of delta 9-tetrahydrocannabinol (THC; 50 mg/kg) reduced plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), while at other times THC had no effect. Administration of THC significantly reduced plasma concentrations of LH and FSH in intact diestrous females. In an additional study, in intact diestrous females injected with testosterone propionate (TP; 125 micrograms), concommitant exposure to THC did not affect plasma testosterone (T) levels, but plasma dihydrotestosterone (DHT) levels at 20 and 60 min were significantly higher in animals receiving TP and THC. Administration of THC can alter pituitary gonadotropin release in intact diestrous and in ovariectomized female mice. Effects of THC on plasma androgen levels after exogeneous treatment with TP suggest that THC can alter metabolism or target tissue response to gonadal steroids.