Reye syndrome is currently viewed as a specific disease entity distinguished from other causes of hepatic failure and encephalopathy on clinical and histologic grounds. A variety of therapeutic approaches, ranging from supportive management to invasive intracranial pressure monitoring and barbiturate-induced coma, have been used because of the wide spectrum of disease progression and severity. Early identification of factors predictive of a poor outcome would be of value in assessing the need for aggressive management. Based on a ten-year experience with 95 patients with Reye syndrome, we suggest that peak plasma ammonia levels are predictive of disease severity and patient survival.