Arginine vasopressin (AVP) and oxytocin (OT) responses during an insulin (0.15 IU/kg body weight) tolerance test (ITT) were evaluated in normal men while they were infused with normal saline, glucose or fructose. Insulin-induced hypoglycemia produced significant plasma AVP and OT increments in the control test. The infusion of fructose was unable to change the posterior pituitary hormonal responses to hypoglycemia. In contrast, AVP and OT responses during ITT were completely abolished when the concomitant infusion of glucose prevented insulin-induced hypoglycemia. These data exclude a direct role of hyperinsulinemia in the mechanism underlying the AVP and OT responses during ITT. Furthermore, since glucose, but not fructose, crosses the blood-brain barrier (BBB), the posterior pituitary hormone responses to hypoglycemia appear to be generated by stimulations of glucosensitive areas located inside the BBB.