Lesions caused by the Côte d'Ivoire subtype of Ebola virus in a naturally infected young chimpanzee were characterized by histopathological and immunohistochemical methods. The predominant lesions consisted of multifocal necrosis in the liver and diffuse fibrinoid necrosis in the red pulp of the spleen. In these sites, macrophages contained large eosinophilic intracytoplasmic inclusion bodies. Immunohistochemical staining indicated that macrophages were a major site of viral replication. The absence of bronchiolar and pulmonary lesions and the paucity of antigen-containing macrophages in the lung suggested that aerosol transmission by this animal was unlikely. There were necrotic foci and antigen-containing macrophages in intestinal lymph nodes, in association with lesions caused by intestinal parasites, suggesting the possibility of virus entry through the digestive tract.