This application continues our efforts to prevent post-traumatic seizures and builds on our 6 years experience in evaluating phenytoin (Dilantin Prophylaxis of Post-traumatic Seizures). That study shows that phenytoin prevents early seizures but is ineffective in preventing late post-traumatic seizures. The present study will examine the effectiveness of valproate in preventing post-traumatic seizures using a randomized, double-blind design. The aims of the study are: 1) to determine whether valproate and phenytoin differ in their effectiveness for preventing early post-traumatic seizures; 2) to determine whether valproate prevents or postpones late post-traumatic seizures; 3) to evaluate the medical, cognitive, emotional and psychosocial side effects of valproate. Patients with severe head injuries with at least 20% chance of developing seizures will be selected. Patients with preexisting conditions that could compromise brain functions (e.g., prior head injury, alcohol abuse, epilepsy, stroke) will be excluded. Experimental group patients will receive a loading dose of valproate within 24 hours of the head injury, and then subsequent daily doses to maintain serum levels within the therapeutic range. Based on the results of the phenytoin study, the control regimen will consist of one week of phenytoin followed by placebo. Patients will take their blinded medication for one year and then be followed for an additional year without any drugs. Incidence of post-traumatic seizures will be determined over two years. In order to assess behavioral side effects of the drug, both groups will undergo neuropsychological evaluations; brief assessments of mood and cognition at 1, 3, 6, 9, and 15 months; and comprehensive cognitive, affective, and psychosocial evaluations at 12 and 15 months post-injury. In summary, this placebo-controlled, randomized clinical trial will attempt to determine the effects of valproate on post-traumatic seizures and on the patients' functioning.