Previous studies have shown that vasopressin potentiates the natriuresis produced by atriopeptin. In five anesthetized dogs of this study, we found that the potentiation was proportional to the dose of vasopressin infused. Sodium excretion was 46±16 μeq/min with atriopeptin (103-126) (AP24) alone (0.36 nmol/kg ± min), was increased to 127±29 by concomitant intravenous infusion of 0.4 mU/kg-mln vasopressin, was further increased to 301±75 by 1.2 μ/kg-min vasopressin and leveled off at 328±37 with 3.6 mU/kg ± min vasopressin. To investigate whether the potentiation by vasopressin was due to an intrarenal action, we infused three doses of vasopressin (0.04, 0.12, and 0.36 mU/kg±min) into the renal artery during intravenous AP24 infusion in a second group of five dogs. The natriuresis, 128±18 μeq/min, was unaffected by any intrarenal dose of vasopressin. In a third group, we determined whether the potentiation produced by vasopressin was mediated by a mechanism involving the renal nerves by denervating the left kidney before AP24 infusion. In the denervated kidneys, sodium excretion was increased from a control value of 33 ±5 μeq/min to 303 ±38 with AP24 alone and was unresponsive to subsequent intravenous vasopressin administration. The exaggerated natriuresis with AP24 alone was of the same magnitude as that produced by AP24 plus the highest doses of intravenous vasopressin in the innervated kidneys of the first group. From these results we conclude that the potentiation of AP-induced natriuresis by vasopressin is mediated by a mechanism involving the renal nerves and probably results from the known effect of vasopressin to inhibit renal nerve activity.