The treatment of 66 children with Reye syndrome proved by hepatic biopsy or autopsy is described. Prior to the utilization of exchange transfusion early in the course of the disease, our case fatality rate was 100% of nine patients. With early diagnosis and early exchange transfusion, the case fatality rate was reduced to 27% of 44 patients. During the 1974 epidemic of Reye syndrome, 26 children were treated. In 18 children the diagnosis was established by hepatic biopsy; 16 received one or more exchange transfusions. There were no deaths among these 26 patients. In the 1974 epidemic, the national case fatality rate was estimated to be 40%. Exchange transfusion appears to have been an important factor in the reduction of the case fatality rate among our patients.