To determine whether antidopaminergic drug administration may modify endogenous opioid activity at the hypothalamic-pituitary level, the effects of naloxone infusion (1.6 mg/h for 4 h) on LH secretion were studied in six postmenopausal women before and after administration of the potent antidopaminergic drug veralipride for 20 days. Before veralipride administration, the naloxone infusion did not alter LH secretion. Chronic administration of veralipride resulted in a significant (P less than 0.01) decline in plasma LH levels. In addition, the naloxone infusion induced a significant (P less than 0.05) increase in plasma LH levels, which reached values similar to those before veralipride administration. These results demonstrate that in postmenopausal women the antidopaminergic drug veralipride can restore, at least in part, the activity of the endogenous opioid system. These findings suggest that endogenous opioid peptides may mediate the inhibitory effect exerted by chronic antidopaminergic drug administration on LH secretion in humans.