A clinico-pathologic correlation can be established for those survivors of Reye syndrome in the higher clinical stages who have sustained irreversible and often major neuropsychiatric deficits. The neuropathologic substrate for the clinical manifestations of mental retardation, recurrent seizures, movement disorders, sensori-motor deficits, psychobiologic maladjustment, and mediocre performance in school and on formal psychometric tests consists of multifocal infarction and astrocytosis in cerebral cortex, diencephalon, basal ganglia, and brainstem. While the mortality rate of Reye syndrome in acute stages is still significantly high (25% in our 20 cases, 52% in the tabulated cases in the higher clinical grades), the occurrence of permanent psychomotor deficits is an equally tragic socioeconomic and medical problem. Of our 15 survivors, 3 have suffered major and 1 has sustained minor brain damage. From a review of the literature, over one-third of survivors are consigned to cerebral malfunction, hence their potential for full enjoyment of life and their intellectual, emotional, and economic contributions to their families and society are sadly curtailed.