The effects on hot flushes of the dopamine antagonist Veralipride versus placebo were investigated in a randomized double-blind study of postmenopausal healthy women (N = 20 in each group). Cutaneous temperature recording and plasma LH pulsatility were studied in eight patients from each group. Veralipride administration (100 mg/day for 30 days) induced a significant (P less than .01) reduction in vasomotor symptoms and was more effective (P less than .05) than placebo. Treatment was followed by the expected increase (P less than .001) in plasma prolactin levels and by a significant decrease (P less than .05) in mean plasma LH. A significant reduction (P less than .01) was observed in objectively recorded hot flushes after Veralipride treatment, whereas there was no significant change in the characteristics of LH pulsatility. Infusion of the opioid antagonist naloxone (N = 5) induced a significant (P less than .01) increase in LH secretion after Veralipride administration. These results suggest that the endogenous opioid system may mediate the endocrine and clinical effects of long-term Veralipride treatment.