In young adult females, estrogen treatment suppresses the cerebrovascular inflammatory response; this is mediated in part via NF-B, a key regulator of inflammatory genes. To examine whether age modifies effects of estrogen on vascular inflammation in the brain, female rats, 3 and 12 months of age, were ovariectomized (OVX); half were treated with estrogen for 4 wk (OE). Cerebral blood vessels were isolated from the animals at 4 and 13 months of age. Inflammation was induced by lipopolysaccharide (LPS), either injected in vivo or incubated with isolated vessels ex vivo. Basal levels of cytoplasmic NF-B were significantly higher in cerebral vessels of young rats, but the ratio of nuclear to cytoplasmic levels was greater in middle-aged animals. LPS exposure increased nuclear NF-B DNA binding activity, protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and production of NO and prostaglandin E₂ (PGE₂) in cerebral vessels. All effects of LPS were markedly greater in vessels from the older animals. Estrogen significantly inhibited the LPS-induced increase in NF-B DNA binding activity in cerebral vessels from animals at both ages. In 4-month-old rats, estrogen also significantly suppressed LPS induction of iNOS and COX-2 proteins, as well as production of NO and PGE₂. In contrast, in 13-month-old females, estrogen had no significant effect on these indices of cerebrovascular inflammation. Thus, the protective, anti-inflammatory effect of estrogen on cerebral blood vessels that is observed in young adults may be attenuated in aged animals, which exhibit a greater overall cerebrovascular response to inflammatory stimuli.