The present study was undertaken in order to establish whether ethanol is able to modify the arginine vasopressin (AVP) response to insulin-induced hypoglycemia in man. In addition, the possible involvement of opioid peptides in the mediation of hypoglycemia and/or ethanol action was investigated. For these purposes, the AVP response to an intravenous (0.15 U/kg) insulin tolerance test (ITT) was measured in 6 normal men treated with saline, naloxone (2 or 4 mg as intravenous bolus plus 5 or 10 mg infused over 105 min), ethanol (50/110 ml of whiskey p.o.), or the combination of ethanol and naloxone. Plasma AVP levels rose by about three-fold during insulin-induced hypoglycemia; administration of naloxone did not modify, whereas ethanol completely abolished the AVP response during ITT. When ethanol was given together with naloxone, AVP rose by only two-fold in response to hypoglycemia. Neither ethanol nor naloxone modified the basal secretion of AVP as tested during 45 min before the ITT. These data demonstrate that ethanol inhibits the AVP response to hypoglycemia. Naloxone-sensitive endogenous opioids do not seem to be involved in the control of basal and hypoglycemia-induced AVP secretion. In contrast, since naloxone partially reversed the inhibiting effects of ethanol, a partial involvement of opioid peptides in ethanol action may be supposed.