Gastrointestinal involvement with histoplasmosis in patients with the acquired immunodeficiency syndrome is a rare but documented phenomenon. Most patients present with diarrhea, fever, and abdominal pain. We present a case of a woman who tested positive for the human immunodeficiency virus antibody who developed an intestinal perforation due to Histoplasma capsulatum of the ileum. The patient, whose only risk factor was a blood transfusion 8 years earlier, had been previously diagnosed as having disseminated histoplasmosis with gastrointestinal involvement. While receiving oral antifungal treatment (itraconazole), she developed two separate areas of ileal perforation due to H capsulatum. Complications from gastrointestinal involvement with histoplasmosis, such as perforation, should be considered in patients infected with the human immunodeficiency virus with signs and symptoms suggesting abdominal disease.