Ischemic cerebral edema has been studied in 41 baboons, with regional cerebral blood flow (CBF) determined by hydrogen clearance, and edema measured by microgravimetry. A threshold of ischemia has been identified for baboon cortex and subcortical white matter, which has to be crossed before edema formation begins. This threshold is 40.5% of normal CBF in cortex, and 34.4% of normal flow in subcortical white matter. A time threshold has also been determined, and the baboon brain can withstand 30 minutes of ischemia of the middle cerebral artery without significant edema formation. Reperfusion of ischemic brain has no effect on tissue water if the ischemic flow and time thresholds have not been crossed. Reperfusion of cortex, where water has begun to accumulate, exacerbates the water accumulation in proportion to the extent of the reperfusion. If these results are applicable to man, restoration of flow should not be attempted after an ischemic insult that reduces flow to less than 40% of normal unless it can be accomplished within 30 minutes of the insult. Provided CBF can be restored to above the 40% threshold within 30 minutes, reversal of the neurological deficit and prevention of ischemic edema can be expected.