The suggestion that schizophrenia may involve a neurodegenerative process has emanated from the highly replicated finding of ventricular enlargement in brain images of patients with this disorder. These investigations have provided a direct impetus for recent histopathologic studies seeking evidence of a neurodegenerative process in the brains of subjects with schizophrenia. Whereas most postmortem studies have reported the presence of atrophy and/or neuronal loss in several corticolimbic regions of subjects with schizophrenia, no quantitative study, to date, has detected an increase in the number of glial cells. For this reason the changes observed in postmortem schizophrenic brain are not consistent with a typical adult pattern of neuronal degeneration, such as that seen in Huntington's disease. Because several studies have reported various changes in layer II of the anterior cingulate, prefrontal, and entorhinal cortices, the histopathologic findings described are compatible with the idea that schizophrenia involves a disturbance of the "inside-out" migration or differentiation of cortical neurons that normally occurs during ontogenesis. A neurodevelopmental perturbation early in life could result in discrete alterations of corticolimbic circuitry that eventually contribute to the appearance of schizophrenic symptoms during adolescence and adulthood.