A review of 65 studies of individuals with schizophrenia who had never been treated with antipsychotic medications indicates significant abnormalities in brain structure and function. Neurological and neuropsychological measures show the most consistent and largest group differences between those affected and normal controls. Measures of structural differences and cerebral metabolic function are significant but less impressive. Electrophysiological differences also are found, but most such studies are older and have methodological problems. The brain abnormalities implicate a variety of interrelated brain regions, primarily the medial temporal, prefrontal, thalamic, and basal ganglia areas. It is concluded that schizophrenia is a brain disease in the same sense that Parkinson's disease and multiple sclerosis are, and that the brain abnormalities in schizophrenia are inherent in the disease process and not medication-related. The challenge for the future is to use the new molecular techniques to study these brain areas and elevate our understanding of schizophrenia's etiology to the next level.