Female reproductive hormones are considered to be protective agents in atherosclerotic vascular disease and stroke. The present study determined if there are unique cerebrovascular responses in female animals to global cerebral ischemia and if 17β-estradiol is important to postischemic outcome in brain. Three groups of anesthetized, sexually mature rabbits were treated with normotensive four-vessel occlusion (6 min) and 3 h of reperfusion: females chronically instrumented with 17β-estradiol implants (EFEM; n = 8, plasma estradiol level = 365 ± 48 pg/ml), untreated females (FEM; n = 8, estradiol = 13 ± 3 pg/ml), and untreated males (M; n = 8, estradiol < limit of radioimmunoassay). CBF (microspheres) and somatosensory evoked potential (SEP) amplitude were measured during ischemia/reperfusion. Baseline hemispheric blood flow and regional flow distribution were not altered by chronic estradiol treatment. Hemispheric blood flow was equivalently reduced during ischemia in FEM and M (6 ± 1 and 9 ± 2 ml min⁻¹ 100 g⁻¹ respectively); however postischemic hyperemia was greater in FEM than M (CBF = 257 ± 27 and 183 ± 27 ml min⁻¹ 100 g⁻¹. However, EFEM experienced higher CBF during ischemia (e.g., 13 ± 2 ml min⁻¹ 100 g⁻¹) and less hyperemia (134 ± 4 ml min⁻¹ 100 g⁻¹ in hemispheres) in numerous brain regions than FEM. CBF at 3 h reperfusion was not different among the groups. Recovery of SEPs was incomplete and similar in all groups. We conclude that chronic exogenous 17β-estradiol treatment increases CBF during global incomplete ischemia and ameliorates postischemic hyperemia in the female animal.