Arginine vasopressin (AVP) is a neurohypophyseal peptide hormone with protean effects. Previous reports had shown that AVP stimulates platelets, but only at concentrations 3-6 logs higher than the normal plasma concentrations in humans. In this study we tested the hypothesis that AVP, at physiologic concentrations, stimulated the expression of an activation-dependent platelet antigen. Platelets obtained from normal volunteers were incubated with increasing concentrations of AVP and the expression of the activation-dependent platelet antigen P-selectin (CD62) was determined by monoclonal antibodies and flow cytometry. There was a concentration-dependent increase in CD62 expression with increasing AVP concentration; at 1 pm AVP, 24.5% (1.3-88.5%) [median (range)] of platelets expressed CD62. The selective vasopressin V1 receptor antagonist d(CH2)(5)-Tyr(me)AVP (TM-AVP) completely abolished AVP-stimulated CD62 expression. We conclude that AVP can activate platelets at concentrations found in normal humans, at least in vitro, and that this response is mediated by the platelet V1 receptor. AVP may be a physiologic platelet agonist.