The purpose of this study was to examine the effects of the kappa opioid receptor agonist U-50,488 and antagonist nor-binaltorphimine (NOR-BNI) on the secretion of prolactin and alpha-melanocyte-stimulating hormone (alpha MSH) in male and female rats. Activation of kappa opioid receptors with U-50,488 increased plasma prolactin concentrations in both male and female rats, whereas blockade of kappa opioid receptors with NOR-BNI decreased plasma prolactin concentrations in male, but not in female rats. U-50,488 also increased and NOR-BNI decreased plasma concentrations of alpha MSH; similar effects were observed in both male and female rats. These results reveal a sexual difference in kappa opioid receptor-mediated regulation of prolactin, but not alpha MSH secretion.