Plasma vasopressin was measured before and after tilt testing in 18 patients with orthostatic hypotension of various causes. In six patients, all of whom had normal osmotic regulation of vasopressin, normal stimulation of vasopressin did not occur on tilt testing; all six had clinical evidence of defects in the afferent or central connections of the baroregulatory reflex arc. In the remaining 12 patients, plasma vasopressin increased to levels appropriate for the degree of hypotension; none of these patients had clinical evidence of defects in afferent or central portions of the baroregulatory arc. Those with subnormal vasopressin response had significantly more severe orthostatic hypotension than the patients with normal vasopressin response, but none had plasma hypotonicity, an abnormality present in one-quarter of those with normal response. It is concluded that the vasopressin response to orthostatic hypotension may serve as a test of the integrity of the afferent and central components of the baroregulatory reflex arc. Furthermore, this study suggests that the normal vasopressin response to orthostatic hypotension may moderate the fall in blood pressure but may adversely affect water balance.