BACKGROUND: While the neuroanatomical underpinnings of the functional brain disconnectivity observed in patients with schizophrenia (SZ) remain elusive, white matter fiber bundles of the brain are a likely candidate, given that they represent the infrastructure for long-distance neural communication. METHODS: This study investigated for diffusion abnormalities in 19 patients with chronic SZ, relative to 19 matched control subjects, across tractography-defined segments of the corpus callosum. Diffusion-weighted images were acquired with 51 noncollinear gradients on a 3T scanner (1.7 mm isotropic voxels). The corpus callosum was extracted by means of whole-brain tractography and automated fiber clustering and was parcelled into six segments on the basis of fiber trajectories. The diffusion indexes of fractional anisotropy (FA) and mode were calculated for each segment. RESULTS: Relative to the healthy control subjects, the SZ patients exhibited mode increases in the parietal fibers, suggesting a relative absence of crossing fibers. Schizophrenia patients also exhibited FA reductions in the frontal fibers, which were underpinned by increases in radial diffusivity, consistent with myelin abnormalities. Significant correlations were observed between patients' degree of reality distortion and their FA and radial diffusivity, such that the most severely psychotic patients were the least abnormal in terms of their frontal fiber diffusivity. CONCLUSIONS: The SZ patients exhibited a variety of diffusion abnormalities in the corpus callosum, which were related to the severity of their psychotic symptoms. To the extent that diffusion abnormalities influence axonal transmission velocities, these results provide support for those theories that emphasize neural timing abnormalities in the etiology of schizophrenia.