This article reports a case of cytomegalovirus (CMV) ileitis with perforation in a woman with transfusion-acquired human immunodeficiency virus (HIV) infection. The clinical problem of small bowel perforation due to CMV disease in association with HIV infection is emphasized. Typically, a patient with a history of chronic diarrhea, fever, and abdominal pain develops the superimposed picture of an acute abdomen and has pneumoperitonium on radiograph. The prognosis is poor.