This study was undertaken to determine the topographical organization of fibers coursing through the human corpus callosum. We correlated the distribution of Wallerian degeneration in the corpus callosum with the anatomical sites of focal cortical lesions due to ischemic infarctions or circumscribed contusions. Fibers from the inferior frontal and anterior inferior parietal regions course through the rostrum and genu of the corpus callosum. Callosal connections from the temporo-parieto-occipital junctional region course through the splenium and caudal portion of the body of the corpus callosum. Both the superior parietal lobule and the occipital cortex give rise to interhemispheric fibers that course exclusively through the splenium of the corpus callosum. No callosal degeneration was associated with a cortical lesion in the anterior superior frontal region. The topographical organization of fibers in the human corpus callosum appears to be fairly similar to that found in the rhesus monkey (Macaca mulatta).