Intravenous infusion of 1-desamino-8-D-arginine vasopressin (DDAVP), an analog of arginine vasopressin (AVP), results in a rise in plasma levels of factor VIII coagulant activity and the von Willebrand factor. DDAVP infusion has been shown to shorten the prolonged bleeding time of patients with inherited platelet defects but the mechanism for this has not been fully clarified. There is little information available on the direct effect of DDAVP on platelets. We examined the effect of DDAVP on platelet responses, including Ca2+ mobilization, to understand the mechanisms by which DDAVP shortens the bleeding time in patients with primary platelet defects. In normal human platelets, DDAVP alone upto 100 microM did not induce aggregation, secretion or a rise in the intracellular Ca2+ concentration, monitored using quin2. In contrast AVP induced all three responses in a dose dependent manner. Interestingly preincubation of platelets with DDAVP at a 100-fold greater concentration inhibited the responses to AVP indicating that DDAVP does interact with the platelets. Moreover, DDAVP did not either potentiate or inhibit the responses to thrombin or ADP. These studies indicate that it is unlikely that the beneficial effect of DDAVP in patients with primary platelet defects is related to a direct stimulatory effect on platelets.