Vascular dysfunction occurs with aging. We hypothesized that oxidative stress and angiotensin II (Ang II, acting via AT₁ receptors) promotes cerebral vascular dysfunction with aging. We studied young (5-6 mo), old (17-19 mo) and very old (23±1 mo) mice. In basilar arteries in vitro, acetylcholine (an endothelium-dependent agonist) produced dilation in young wild-type mice that was reduced by ~60 and 90% (P<0.05) in old and very old mice, respectively. Similar effects were seen using A23187, a second endothelium-dependent agonist. The vascular response to acetylcholine in very old mice was almost completely restored with tempol (a scavenger of superoxide) and partly restored by PJ34, an inhibitor of poly (ADP-ribose) polymerase (PARP). We used mice deficient in Mn-superoxide dismutase (Mn-SOD^+/-) to test whether this form of SOD protected during aging but found that age-induced endothelial dysfunction was not altered by Mn-SOD deficiency. Cerebral vascular responses were similar in young mice lacking AT₁ receptors (AT₁^-/-) and wild-type mice. Vascular responses to acetylcholine and A23187 were reduced by ~50% in old wild-type mice (P<0.05) but were normal in old AT1 deficient mice. Thus, aging produces marked endothelial dysfunction in a cerebral artery that is mediated by reactive oxygen species, may involve activation of PARP, but was not enhanced by Mn-SOD deficiency. Our findings suggest a novel and fundamental role for Ang II and AT₁ receptors in age-induced vascular dysfunction.