Background: Current investigations suggest that brain white matter may be qualitatively altered in schizophrenia even in the face of normal white matter volume. Diffusion tensor imaging provides a new approach for quantifying the directional coherence and possibly connectivity of white matter fibers in vivo. Methods: Ten men who were veterans of the US Armed Forces and met the DSM-IV criteria for schizophrenia and 10 healthy, age- matched control men were scanned using magnetic resonance diffusion tensor imaging and magnetic resonance structural imaging. Results: Relative to controls, the patients with schizophrenia exhibited lower anisotropy in white matter, despite absence of a white matter volume deficit. In contrast to the white matter pattern, gray matter anisotropy did not distinguish the groups, even though the patients with schizophrenia had a significant gray matter volume deficit. The abnormal white matter anisotropy in patients with schizophrenia was present in both hemispheres and was widespread, extending from the frontal to occipital brain regions. Conclusions: Despite the small sample size, diffusion tensor imaging was powerful enough to yield significant group differences, indicating widespread alteration in brain white matter integrity but not necessarily white matter volume in schizophrenia.