Serial studies on serum enzyme and isoenzyme abnormalities in seven cases of Reye's syndrome were found to segregate patients into three categories of organ involvement. The patients with both extensive hepatic and previously unrecognized skeletal muscle involvement died despite therapeutic measures. The other two groups were characterized by enzyme and isoenzyme changes consistent with either predominantly muscular or hepatic involvement. The prognostic value of these abnormalities has been substantiated in subsequent cases of this syndrome. These findings suggest that those patients at greatest risk may be identified early, thus improving evaluation of the efficacy of specific therapeutic interventions in this disease.