The present study was undertaken to determine if the neuroprotective effect of 17β-estradiol (E2) when administrated after ischemia is dose-dependent and if the therapeutic window for estrogen can be prolonged. Ischemic injury was induced by permanent middle cerebral artery occlusion (p-MCAO). Administration of E2 at 30 min after ischemia resulted in a reduction in lesion volume. A higher dose of E2 extended the therapeutic window to 6 h after cerebral ischemia in 33% of the rats. These findings suggest that postischemic treatment with estrogen affords protection against ischemic damage and that it acts within a clinically useful therapeutic window.