Evidence from both clinical and pathological investigations suggests that increased intracranial pressure (ICP) is a significant factor in the mortality of patients with Reye's syndrome. This, coupled with a critical review of our previous 22 patients, which failed to document the efficacy of exchange transfusion, led us to include continuous ventricular pressure monitoring in the supportive care of children with Reye's syndrome. To date, three children, ages 3 to 5 years, have been managed with continuous ICP monitoring. All had stage IV coma by both clinical and electroencephalographic criteria. Peak blood ammonia concentrations were 1,036, 316, and 560µg/100 ml; all had elevations of serum glutamic oxaloacetic transaminase level, prothrombin time, and creatine phosphokinase level as well. Rapid, unpredictable increases in ICP occurred for many days in all children. Therapeutic measures most successful in controlling ICP were the intravenous administration of mannitol and hyperventilation. Elevations in ICP occurred despite serum osmolality as high as 418 mOsm and following oral administration of glycerol. Rapid increases in ICP also resulted from routine manipulation of the patients (e.g., postural drainage). Exchange transfusion, used in two of the three patients, increased ICP in one child and had no effect in the other. All three children have achieved complete recovery and are doing well 6 months after their illness. Our experience with these children suggests that vigorous supportive therapy, including careful monitoring of ICP, should be used as a basis of comparison when evaluating claims of specific treatment in Reye's syndrome.