Progesterone is a potent hormone acting on the female reproductive tract and influencing a series of other functions. Recent studies revealed a correlation between progesterone and brain neurotransmitters and neuropeptides. Our study evaluated the possible effect of norgestimate, a new progestin, on hypothalamic and pituitary beta-endorphin (B-EP) concentration in castrated female rats. Ovariectomy was performed under ethyl ether anesthesia. Treatment was started 3 weeks after surgery. Norgestimate, estradiol benzoate or norgestimate plus estradiol benzoate were administered. The two steroids were dissolved in sesame oil and injected (s.c.) every day for 2 weeks. Pituitary and hypothalamus B-EP concentrations were measured by radioimmunoassay. Our studies showed that norgestimate increases the pituitary and hypothalamic B-EP concentration in female rats, reaching values higher than controls and estrogen-treated rats. Because B-EP has an important role in reproductive function, both modulating gonadotropin secretion and sexual behavior, the present results lead to the hypothesis that norgestimate affecting B-EP concentrations may influence central functions.