The antidiuretic hormone arginine vasopressin interacts with two types of receptors: V1, which mediates the effects of vasopressin on vascular smooth muscle, and V2, which mediates the antidiuretic effects on renal tubules. Resistance of the renal tubules to arginine vasopressin and to the antidiuretic V2-specific agonist 1-desamino[8-D-arginine] vasopressin (dDAVP) occurs in congenital nephrogenic diabetes insipidus, a rare X-linked disease, although the V1-receptor responses remain intact. The extrarenal actions of dDAVP in normal persons are a decrease in blood pressure, an increase in plasma renin activity, and stimulation of the release of factor VIIIc and von Willebrand factor. We measured the response of mean arterial pressure, pulse rate, plasma renin activity, factor VIIIc, and von Willebrand factor to an infusion of dDAVP (0.3 microgram per kilogram of body weight) in seven male patients with congenital nephrogenic diabetes insipidus, six obligatory carriers of the gene for nephrogenic diabetes insipidus, five patients with central diabetes insipidus, and four normal subjects. In the normal subjects and the patients with central diabetes insipidus, dDAVP decreased mean arterial pressure (by 10 to 15 percent) and increased pulse rate (by 20 to 25 percent), renin activity (by 65 percent), and the release of coagulation factors (twofold to threefold) (all changes were significant, P less than 0.01). None of these changes were observed in the patients with congenital nephrogenic diabetes insipidus, and minimal responses were observed in the obligatory carriers. These results confirm the existence of extrarenal vasopressin V2-like receptors, which may be defective in patients with congenital nephrogenic diabetes insipidus.