THE EFFECTS OF phenytoin, carbamazepine and valproic acid on alterations in sodium-potassium-adenosine triphosphatase activity during ischemia were studied in the rat brain. Pretreatment with phenytoin and carbamazepine prevented a reduction of this activity, which, without either treatment, was observed in the cerebral hemisphere exposed to 30-minute ischemia resulting from unilateral middle cerebral artery occlusion. Valproic acid, on the other hand, did not principally affect the ischemic impairment of this membrane-bound enzyme activity. These results lend support to the previously proposed use of phenytoin in cerebral ischemia, but also suggest the therapeutic availability of another common anticonvulsant, carbamazepine, for treatment of the insult.