Of 40 patients with Reye syndrome hospitalized over a three-year period, 17 died, while two survivors have severe neurologic impairment. The illness progressed through five stages, each correlating with progressive rostral-caudal central nervous system involvement. Clinical indexes suggesting a poor outcome included an initial blood ammonia concentration > 300μg/100 ml; a rapid progression through the first three clinical stages; the onset of seizure activity in stage III; increased cerebrospinal fluid pressure in stage IV; and a prothrombin time in stage III that was 13 or more seconds longer than that of the control. In patients with an illness beyond stage III, death or severe neurological impairment occurred. The mortality did not seem to be lowered by exchange transfusion or conventional medical therapeutic means of reducing increased intracranial pressure.