Histoplasma capsulatum var. capsulatum is endemic to the central United States, especially within the Ohio, Missouri, and Mississippi river valleys; other endemic areas in the Western hemisphere include Mexico, Guatemala, Peru, and Venezuela. Histoplasmosis has been reported in many non-endemic areas as well. It is most plentiful in soil enriched by avian or bat droppings. It has a marked affinity for dissemination through the mononuclear phagocyte system, and gastrointestinal involvement occurs in more than 80% of patients with disseminated infection. Isolated gastrointestinal histoplasmosis has been reported rarely. Although most patients with disseminated histoplasmosis are immunocompromised, dissemination can occur in apparently immunocompetent hosts. Of note, it is the most common endemic mycosis in patients with AIDS. Histoplasmosis has also been described in association with infliximab therapy, an anti-tumor necrosis factor alpha drug used in the treatment of Crohn’s disease and rheumatoid arthritis.