This is a critical review and integration of recent evidence demonstrating the frequency, type, and clinical significance of brain dysfunction in schizophrenia. Neuroradiological, neurophysiological, and neuropsychological data suggest brain impairment in at least 20% to 35% of schizophrenic patients. The abnormalities are nonspecific and can result from a variety of causes. Preliminary evidence suggests that there are two or more syndromes that differ in severity and type of brain abnormality, rather than a unitary schizophrenic illness. A complex, variable picture of brain dysfunction, including ventricular enlargement and cerebral atrophy, disturbances of cerebral metabolism, neuropsychologic deficits, and neurologic "soft" signs, is found especially in chronically impaired schizophrenics with "negative" symptoms. Extent and locus of dysfunction in a corticosubcortical arousal-attention system involving areas of the frontal cortex, limbic system, and brain stem reticular formation are hypothesized to determine the relative prominence of "positive" and "negative" symptoms. Future research on neuroanatomy, etiology, and treatment must take into account the heterogeneity of the schizophrenias and might fruitfully utilize the positive-negative dimension.