OBJECTIVE: The aim of this study was to explore the microstructural integrity of whole-brain white matter by diffusion tensor imaging in first-episode, treatment-naive young adults with major depressive disorder. METHOD: Diffusion tensor imaging scans were obtained from 14 first-episode, treatment-naive young adult patients with major depressive disorder and 14 healthy comparison subjects. A voxel-based method was used to analyze the scans. RESULTS: The patient group exhibited significantly lower fractional anisotropy values than healthy comparison subjects in the white matter of the right middle frontal gyrus, the left lateral occipitotemporal gyrus, and the subgyral and angular gyri of the right parietal lobe. There were no regions of significantly higher fractional anisotropy values in patients compared with healthy comparison subjects. CONCLUSIONS: These findings suggest that abnormalities of brain white matter may be present early in the course of major depressive disorder. They also support the idea that white matter lesions may disrupt the neural circuits involved in mood regulation and thus contribute to the neuropathology of major depressive disorder.