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We report the first apparent case of a splenectomized individual who developed severe trypanosomiasis with central nervous system involvement. The patient was a 41-year-old man who participated in an east African safari. Upon his return to the United States, the patient presented with an infection with Trypanosoma brucei rhodesiense that was treated successfully with suramin and melarsoprol. The onset of symptoms, laboratory studies, and disease progression did not differ from previously reported cases in the literature. The role of the spleen in trypanosomiasis is not well understood and the few reports available describe only animal models. This report suggests that asplenia had no apparent effect on the onset of symptoms and overall severity of illness. Further studies are necessary to ultimately define the role of the spleen in trypanosomiasis.