An awake-primate model has been developed which permits reversible middle cerebral artery (MCA) occlusion during physiological monitoring. This method eliminates the ischemia-modifying effects of anesthesia, and permits correlation of neurological function with cerebral blood flow (CBF) and neuropathology. The model was used to assess the brain's tolerance to focal cerebral ischemia. The MCA was occluded for 15 or 30 minutes, 2 to 3 hours, or permanently. Serial monitoring evaluated neurological function, local CBF (hydrogen clearance), and other physiological parameters (blood pressure, blood gases, and intracranial pressure). After 2 weeks, neuropathological evaluation identified infarcts and their relation to blood flow recording sites. Middle cerebral artery occlusion usually caused substantial decreases in local CBF. Variable reduction in flow correlated directly with the variable severity of deficit. Release of occlusion at up to 3 hours led to clinical improvement. Pathological examination showed microscopic foci of infarction after 15 to 30 minutes of ischemia, moderate to large infarcts after 2 to 3 hours of ischemia, and in most cases large infarcts after permanent MCA occlusion. Local CBF appeared to define thresholds for paralysis and infarction. When local flow dropped below about 23 cc/100 gm/min, reversible paralysis occurred. When local flow fell below 10 to 12 cc/100 gm/min for 2 to 3 hours or below 17 to 18 cc/100 gm/min during permanent occlusion, irreversible local damage was observed. These studies imply that some cases of acute hemiplegia, with blood flow in the paralysis range, might be improved by surgical revascularization. Studies of local CBF might help identify suitable cases for emergency revascularization.