In order to establish whether melatonin alters basal and/or stimulated oxytocin secretion, 18 normal men were treated (p.o.) with 6 or 12 mg melatonin or placebo in basal conditions (N-6 subjects) or concomitantly to the administration of insulin (O.15 IU/kg body weight in an i.v. bolus) (N-6 subjects) or angiotensin II (increasing doses of 4, 8 and 16 ng/kg/min, at intervals of 20 min). The administration of 6 or 12 mg melatonin did not change basal and angiotensin II-stimulated oxytocin secretion. In contrast, the oxytocin response to insulin-induced hypoglycemia was significantly reduced by melatonin treatment. In fact, the mean peak oxytocin response to hypoglycemia was 2.2 times higher than baseline in the absence of melatonin, whereas it was 1.6 times higher than basal value after administration of 6 or 12 mg melatonin. These data indicate an involvement of melatonin in the regulation of the oxytocin response to hypoglycemia in normal men. The lack of effects of melatonin on basal and angiotensin II-stimulated oxytocin secretion argues against the possibility that melatonin exerts an overall modulatory role on oxytocin secretion in humans.