Histologic sections were made from selected regions of the brains of 25 schizophrenic patients aged 21 to 54 years (mean, 43.5 years) who died during their hospitalization at St Elizabeths Hospital, Washington, DC. These sections were compared with similarly prepared sections from the same brain regions of 28 nonschizophrenic patients of similar age, who were hospitalized and died at the same hospital during the same period, and with sections from 20 age-matched, nonpsychiatric patients who died in a general hospital. Although few differences were apparent in material from schizophrenic and nonpsychiatric cases in sections stained for cellular structures, myelin, or axis cylinders, Holzer's stain for glial fibrils demonstrated increased fibrillary gliosis that affected principally the periventricular structures of the diencephalon, the periaqueductal region of the mesencephalon, or the basal forebrain in three fourths of the brains from schizophrenic subjects. Hypothalamus, midbrain tegmentum, and substantia innominata were most often affected. The nature and distribution of the findings suggest previous or low-grade inflammation. Review of the clinical history and course of each case allows some correlations to be made between clinical signs and histopathologic data.