—The renin-angiotensin system is a major physiological regulator of body fluid volume, electrolyte balance, and arterial pressure. Virtually all of the biological actions of the principle effector peptide angiotensin II (ANG II) have been attributed to an action at the type 1 (AT₁) ANG receptor. Until recently, the functional role of the type 2 (AT₂) receptor, if any, has been unknown, possibly because the AT₂ receptor has a low degree of expression compared with that of the AT₁ receptor. Evidence has now accumulated that the AT₂ receptor opposes functions mediated by the AT₁ receptor. Whereas the AT₁ receptor stimulates cell proliferation, the AT₂ receptor inhibits proliferation and promotes cell differentiation. These differences in growth responses have been ascribed to different cell signaling pathways in which the AT₁ receptor stimulates protein phosphorylation and the AT₂ receptor dephosphorylation. During the past 5 years, studies have demonstrated that the AT₂ receptor is responsible for vasodilation and natriuresis, thus opposing the vasoconstrictor and antinatriuretic effects of ANG II mediated through the AT₁ receptor. Work from our laboratory and others indicates that the AT₂ receptor stimulates vasodilation and natriuresis by an autocrine cascade including bradykinin, nitric oxide, and cyclic GMP. The AT₂ receptor also has been found to control vasodilator prostaglandins, which have a role in blood pressure regulation. The AT₂ receptor appears to play a counterregulatory protective role in the regulation of blood pressure and sodium excretion that opposes the AT₁ receptor.