No large case series of gastrointestinal histoplasmosis (GIH) in patients with AIDS has been published. We report 18 cases and review 34 published cases in the medical literature. We did a retrospective chart review from patients seen in our medical practices between 1989 and 2004. Most of our patients were men who had sex with men and who were not receiving highly active antiretroviral therapy. Median CD4 count was 34/muL. The most common presenting symptoms were diarrhea, fever, abdominal pain, and weight loss. The most commonly involved site was the colon or cecum. Biopsies revealed visible Histoplasma capsulatum organisms in 89%. Cultures from any site were positive in 76.9%. Four patients died from GIH. Gastrointestinal histoplasmosis occurs in severely immunocompromised patients with AIDS not receiving highly active antiretroviral therapy. Typical manifestations include diarrhea, fever, abdominal pain, and weight loss. Diagnosis is confirmed by blood or gastrointestinal tissue culture. Improvements in antiretroviral and antifungal therapies appear to have reduced the incidence of GIH and may improve the prognosis of this disease.