Despite a large body of experimental evidence suggesting that posttraumatic epilepsy can be prevented, there is no generally accepted pharmacological regimen for posttraumatic seizure prophylaxis. This article describes a phenytoin anticonvulsant regimen specifically tailored for the patient with acute head injury and designed to provide immediate and sustained plasma concentrations of phenytoin between 10 and 20 microgram/ml. Initially, an intravenous phenytoin dose of 11 mg/kg body weight is immediately followed by an intramuscular dose of 13 mg/kg body weight. This is followed by daily intramuscular maintenance doses, usually 8.8 mg/kg body weight, until oral medication can be tolerated. Maintenance dosage adjustments, when necessary, are based on serial plasma concentrations of the drug. Eighty-four patients with severe head injuries with substantial risk of posttraumatic epilepsy were administered this regimen. Only 6% of these patients had seizures during the first year after injury (first week excluded), and this is considerably less than the rates reported elsewhere in the literature. Only one-third of these patients are known to have continued to take phenytoin after the first month, and only half of these had plasma phenytoin concentrations above the desired minimal level. The greatly reduced incidence of posttraumatic seizures in these patients, despite the low rate of long-term drug compliance, suggests that a prophylactic effect, rather than a suppressive effect, is produced.