Background: Cytomegalovirus colitis is an important complication of the acquired immunodeficiency syndrome (AIDS), although the clinical and colonoscopic manifestations of this disease have not been systematically characterized. Methods: Patients with AIDS and cytomegalovirus colitis were prospectively identified at two medical centers. The diagnosis of cytomegalovirus disease was based on established endoscopic and histologic criteria. At the time of sigmoidoscopic and/or colonoscopic examination, clinical features were recorded; the location, size, and appearance of all endoscopic abnormalities were documented; and multiple biopsies of any lesions were performed. Results: Fifty-six patients were studied. The majority of the patients were homosexual men with severe immunodeficiency (median CD4 lymphocyte count 15/mm3, range 1 to 294/mm3). Chronic diarrhea and abdominal pain were the most frequent clinical manifestations, seen in 45 (80%) and 28 (50%) patients, respectively. Five patients (9%) presented with lower gastrointestinal hemorrhage, three of whom had no antecedent history of diarrhea. The colonoscopic abnormalities could be categorized into three main groups: colitis associated with ulcer (39%), ulceration alone (38%), or colitis alone (20%). Subepithelial hemorrhage was a prominent endoscopic manifestation of disease. Of the 31 patients undergoing colonoscopy to the cecum, in four (13%) endoscopic evidence of disease was limited to the colon proximal to the splenic flexure. Conclusions: Cytomegalovirus colitis in AIDS appears to have variable but stereotypical clinical and colonoscopic manifestations. Distal colitis associated with ulceration is the most common colonoscopic pattern.