The effect of thiopental in ameliorating permanent brain damage in rhesus monkeys after 16 min of global ischemia of the brain produced by a high-pressure neck tourniquet and systemic arterial hypotension was studied. Intensive care and life support, including monitoring of physiologic variables, were provided for 7 days after ischemia. Neurologic recovery was evaluated by scoring neurologic deficit and by histopathologic examination of the brain at sacrifice on day 7 after ischemia. Ten control monkeys had a mean neurologic deficit score of 53 .+-. 15% (mean .+-. SEM [standard error of the mean]). Thiopental, 90 mg/kg, administered 5 and 15 min after ischemia significantly improved neurologic recovery, with neurologic deficit scores of 0 (n = 5) and 18 .+-. 8% (n = 5), respectively. Improved neurologic recovery was not observed when therapy was delayed to 30 and 60 min after ischemia. Thiopental, 120 mg/kg, improved recovery when administered 60 min (neurologic deficit score, 7 .+-. 6%), but not 30 min after ischemia. Histologic changes in the brain correlated with neurologic deficit scores. After 16 min of global ischemia of the brain, a major portion of the permanent brain damage occurs after restoration of circulation and is amenable to therapy with thiopental. A dose- and time-related response to thiopental therapy is apparent, but the optimal values were not identified.