The influence of 1-deamino-8-D-arginine vasopressin (DDAVP), the new antidiutetic polypeptide without any side effects on plasma cortisol, was investigated in 30 healthy persons. A dose of 4 mug DDAVP administered intravenously induced a rise in plasma cortisol (hydrocortisone) levels greater than 3.5 mug/100 ml in 12 out of 20 persons studied. In this group (group I), the average increase at 15 minutes was 6.92+/-1.74 mug/100 ml (P less than 0.005), while in the remaining eight persons (group II) plasma cortisol levels decreased according to the usual normal daily rhythm. DDAVP, 80 mug, administered intranasally had no demonstrable influence on physiologic plasma cortisol regulation. On the basis of the present findings with relatively low doses, pituitary responsiveness (ACTH release) might be expected to occur in a higher percentage of persons after giving high intravenous doses of DDAVP. Further efforts are necessary to develop a safe vasopressin test for clinical examination of adenohypophyseal function.