Marchiafava-Bignami disease was diagnosed postmortem in a 39-year-old man who drank excessive amounts of white port wine. This is the fifth report of the disease in a native North-American with no Italian ancestry. The lesion involved the corpus callosum and hippocampal commissure but spared the anterior commissure, middle cerebellar peduncles, optic chiasm, and centrum semiovale. Wernicke-Korsakoff encephalopathy and pellagroid neuronal changes were also present.