In severe Reye's syndrome, with nonspecific intensive supportive therapy, the mortality rate approaches 75%. In many instances, death is due to uncontrolled cerebral edema and elevated intracranial pressure (ICP). Pentobarbital therapy, sufficient to maintain a blood barbiturate level between 2.5 mg% and 4.0 mg%, was used to control ICP in seven patients with metabolic coma complicated by intracranial hypertension (intracranial pressure > 30 mm Hg for 30 min). The nadir of their neurological function was characterized by no response to deep pain, absent or abnormal oculocephalic responses, bilaterally dilated, unreactive pupils, and markedly irregular or absent respirations. Before barbiturate administration hyperventilation, steroids, mannitol, and other supportive therapies commonly used in Reye's syndrome were begun. After institution of pentobarbital therapy, the daily mannitol dose required to maintain the intracranial pressure below 20 mm Hg was significantly reduced (p< 0.001), from 3.7 ± 0.3 to 0.5 ± 0.2 g/kg/day. All the patients survived, and six have no obvious neurological sequelae. Pentobarbital is a useful adjunct for intracranial pressure control in advanced metabolic coma.