We investigated the temporal profile for neuropathologic outcomes after cerebral ischemia using a rat model of reversible middle cerebral artery occlusion, where reperfusion can be introduced in nonanesthetized rats. Reperfusion was performed 1 hour to 5 hours after the occlusion. Control animals underwent permanent occlusion. The results indicate that the time window to reduce infarct volume is 2 hours, and that a > or = 3-hour duration of ischemia is sufficient to attain the maximal infarction observed after permanent ischemia. This suggests that any therapies that follow the therapeutic window will provide little benefit for transient cerebral ischemia and reperfusion injury.