The microstructural integrity of the corpus callosum (CC) in first-episode schizophrenia patients was assessed by measuring the signal intensity (SI) in T1-weighted MRI images. Analyses revealed that compared to both healthy controls and non-schizophrenic patients, schizophrenia patients showed reductions in SI in all the callosal subregions, the genu, body, isthmus and splenium in first-episode schizophrenia. These results indicate that schizophrenia is characterized by pathology of this principal interhemispheric commissure; the abnormalities may reflect distributed (rather than localized) interhemispheric disconnectivity that extends beyond the heteromodal association cortices.