Cytomegalovirus infection is usually reported in immunocompromised patients. In this study, 19 patients with cytomegalovirus (CMV) infection of the alimentary tract were reviewed, none of whom had acquired immunodeficiency syndrome. The patients' sex distribution was similar, and their ages ranged from 22 to 84 yr (mean = 61 yr). Only four patients had underlying diseases resulting in immunocompromise. The most common presentation was gastrointestinal bleeding, which occurred in 11 of the 19 patients (58%). Two patients had an unusual presentation of obstructive jaundice due to exuberant growth of granulation tissue at the ampulla of Vater. The majority of the lesions (n = 23) occurred in the large intestine and duodenum. Sixteen of these 23 lesions (69.6%) showed ulceration. Of these 16 lesions, six were diagnosed macroscopically as malignant by the endoscopists. It was observed histologically that a predominant epithelial distribution of the CMV inclusion bodies was associated with no or only mild inflammation, whereas a predominant endothelial distribution of the inclusion bodies was associated with ulcerative, severely inflamed lesions. From these observations, we conclude that ulceration probably is due to an ischemic process resulting from narrowing of capillary lumens by swollen endothelial cells affected by CMV infection. Concomitant infection by Candida species was found in only one patient. One patient had coexistent ulcerative colitis while another also suffered from graft-versus-host disease after bone marrow transplantation. In five of the eight cases with follow-up biopsies, the CMV inclusion bodies disappeared in subsequent biopsies. To conclude, a high degree of alertness is required for the histological diagnosis of unexpected CMV infection of the alimentary tract, in order to warrant correct treatment for the patients.