Normal aging and chronic alcoholism result in disruption of brain white matter microstructure that does not typically cause complete lesions but may underlie degradation of functions requiring interhemispheric information transfer. We examined whether the microstructural integrity of the corpus callosum assessed with diffusion tensor imaging (DTI) would relate to interhemispheric processing speed. DTI yields estimates of fractional anisotropy (FA), a measure of orientation and intravoxel coherence of water diffusion usually in white matter fibers, and diffusivity (<D>), a measure of the amount of intracellular and extracellular fluid diffusion. We tested the hypothesis that FA and <D> would be correlated with (i) the crossed-uncrossed difference (CUD), testing visuomotor interhemispheric transfer; and (ii) the redundant targets effect (RTE), testing parallel processing of visual information presented to each cerebral hemisphere. FA was lower and <D> higher in alcoholics than in controls. In controls but not alcoholics, large CUDs correlated with low FA and high <D> in total corpus callosum and regionally in the genu and splenium. In alcoholics but not controls, small RTEs, elicited with equiluminant stimuli, correlated with low FA in genu and splenium and high <D> in the callosal body. The results provide in vivo evidence for disruption of corpus callosum microstructure in normal aging and alcoholism that has functional ramifications for efficiency in interhemispheric processing.