The effect of bifemelane hydrochloride on plasma beta-endorphin-like immunoreactivity (beta-En-LI) levels in rats was studied. Bifemelane hydrochloride (25 mg/kg) was injected i.p., and the animals were decapitated at various times after the administration. The plasma beta-En-LI levels were measured by radioimmunoassay. The effect of bifemelane hydrochloride on beta-En-LI release from the anterior pituitary was also investigated by means of an in vitro experiment. The beta-En-LI content in the hypothalamus and pituitary gland did not change significantly after bifemelane hydrochloride injection. The plasma beta-En-LI levels decreased significantly in a dose-related manner with a nadir at 40 min after the injection. The beta-En-LI release in vitro from the anterior pituitary was inhibited with the addition of bifemelane hydrochloride. The findings suggest that bifemelane hydrochloride acts on the anterior pituitary to inhibit beta-En-LI release.