The authors studied the effect of thiopental in ameliorating permanent brain damage in monkeys after 16 min of global ischemia of the brain produced by a high-pressure neck tourniquet and systemic arterial hypotension. Intensive care and life support, including monitoring of physiologic variables, were provided for seven 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 per cent (mean ± SEM). 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 per cent (n = 5), respectively. Improved neurologic recovery was not observed when therapy was delayed to 30 and 60 min after ischemia. However, thiopental, 120 mg/kg, improved recovery when administered 60 min (neurologic deficit score, 7 ± 6 per cent), but not 30 min after ischemia. Histologic changes in the brain correlated with neurologic deficit scores. These results show that 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. There appears to be a doseand time-related response to thiopental therapy, but the optimal values were not identified in this study.