Insulin-induced hypoglycemia causes somnolence in rhesus monkeys, a phenomenon usually considered an aspecific consequence of neuroglycopenia. Previous observations from our laboratory have raised the possibility that arginine vasopressin (AVP) may also play a role in this decrease in wakefulness. In the present study we tested this hypothesis by inducing hypoglycemia (approximately 40 mg/dl) in ovariectomized rhesus monkeys by intravenous administration of insulin in the presence of continuous intracerebroventricular infusions of the V1 receptor antagonist [deamino-Pen1, O-Me-Tyr2,Arg8]-vasopressin (180 micrograms/60 microliters per h) or of its vehicle alone (artificial cerebrospinal fluid, 60 microliters/h). Wakefulness was assessed by a scoring system by observers blinded to the experimental protocol. The AVP antagonist significantly attenuated the decrease in wakefulness observed in response to insulin-induced hypoglycemia (p < .03) without increasing blood glucose levels. These and previous findings suggest that the somnolence induced by a moderate degree of hypoglycemia may not entirely be the direct consequence of neuroglycopenia and that AVP may, directly or indirectly, be involved.