Thirty-six patients with Reye syndrome were admitted to St. Louis Children's Hospital during a ten-year period from January, 1966, through June, 1975; ten patients (28%) died. Seven (64%) of the ten deaths occurred in the 11 patients admitted between 1966 and 1971, whereas only three (12%) of 25 patients died thereafter. We attribute this reduction in case fatality rate to early diagnosis, recognition of milder cases, and intensive medical support including continuous intravenous infusion of hypertonic glucose, intermittent infusion of hypertonic mannitol, and early elective endotracheal intubation. Analyses of metabolic, hormonal, and blood gas data obtained serially during the acute illness in 16 of these patients provide a basis for a discussion of the pathophysiology of this disorder.