In a double-blind trial of phenytoin for the prevention of postoperative epilepsy in craniotomy patients, epilepsy was observed in 7.9% (8/101) of patients treated with phenytoin and in 16.7% (17/102) of those receiving placebo. Therapeutic drug levels were associated with a significant reduction in the frequency of epilepsy. Three-quarters of the fits occurred within a month of cranial surgery. High rates of epilepsy have been observed after cranial surgery in patients with meningioma, aneurysm, and head injury with or without intracranial clots, and routine prophylaxis with phenytoin would seem to be indicated in such patients.