We present a case of colonic histoplasmosis in a young HIV antibody-positive homosexual male who presented with acute diarrhea. The diagnosis was made by flexible sigmoidoscopy with biopsy which revealed organisms morphologically consistent with Histoplasma capsulatum, and was later confirmed by fungal culture of the biopsy specimens. At colonoscopy, skip areas with plaques, ulcers, and a pseudopolyp were observed. The colitis resolved endoscopically after a 6-wk course of intravenous amphotericin B, and the patient has had no recurrence of symptoms while on maintenance therapy with amphotericin B. However, the organisms continue to be noted on biopsies of normal-appearing areas in the rectum and sigmoid 5 months after diagnosis. Colonic involvement with H. capsulatum, an organism endemic to the Midwest, may be seen more frequently as the total number of cases of HIV-infected individuals increases in this region.