To investigate whether vasopressin is involved in the secretory mechanism of atrial natriuretic polypeptide (ANP), effects of arginine-vasopressin (AVP) administered iv on plasma ANP levels were studied in conscious, unrestrained rats. The administration of 100 ng and 1 ug of AVP caused a dose-dependent increase of the plasma ANP level, which was blocked by a V1-receptor antagonist of AVP, and was attenuated by 5 ml blood volume reduction before the stimulation. The injection of less than 10 ng of AVP induced no significant effects on ANP secretion. However, the administration of 5 ng of AVP significantly enhanced ANP secretion induced by intravascular volume expansion with 3 ml saline infusion. These results suggest the possible physiological significance of AVP as a modulator rather than a direct stimulator of ANP secretion from the heart.