We have investigated the issue of sexual dimorphism in the secretion of vasopressin, its pressor action, and the development of deoxycorticosterone (DOC)-salt hypertension. In normal human subjects on controlled salt intake, the basal secretion of vasopressin, indicated by plasma vasopressin levels and urinary excretion of vasopressin, was higher in men than in women and in blacks than in whites. Basal vasopressin secretion also was higher in male than in female rats. This effect was not associated with a difference in the metabolic clearance of the hormone. The sex-related difference in vasopressin release in rats was abolished by gonadectomy and restored by treatment of males with testosterone and females with ovarian hormones. The pressor responsiveness to vasopressin was higher in male than in randomly cycling female rats. Finally, DOC-salt hypertension, which is dependent on vasopressin, developed more rapidly in male than in female rats. Although there was no sex-related difference in the extent to which plasma vasopressin levels were elevated, pressor responsiveness to vasopressin was greater and baroreflex sensitivity was attenuated to a lesser extent in hypertensive males than in hypertensive females. Thus, it seems likely that gonadal hormones play a significant role in cardiovascular regulation.