Examination with magnetic resonance imaging of 40 patients with confirmed diagnoses of multiple sclerosis showed that corpus callosum involvement is common. Thirty percent of the patients had focal callosal lesions similar to those described in the pathology literature. Long, inner callosal-subcallosal lesions were found in 55% of patients. These lesions had signal characteristics similar to those of noncallosal periventricular lesions. Diffuse moderate to severe atrophy of the corpus callosum was noted in 40% of patients, with one exception concurrent with inner callosal lesions. The nature of the inner callosal lesions is not known, since these lesions are not typically described in the literature. These lesions may represent demyelination or increased water content and may be the precursor to atrophy that progresses from the ependymal surface toward the outer fibers of the corpus callosum.