A patient with adult T-cell leukemia-lymphoma suffered a jejunal perforation, which we believe was directly attributable to cytomegalovirus (CMV) infection. In the areas of ulceration and perforation in the small bowel, blood vessels penetrating the muscularis propria showed extensive lining of cytomegalic endothelial cells with CMV inclusions, accompanied by occasional disruption of the walls, partial occlusion of the lumina, fibrin thrombi, and hemorrhage. The CMV-induced vascular damage seemed to be closely related to the occurrence of ulcers and perforation. The recognition of CMV as a cause of lethal gastrointestinal lesions in immunocompromised hosts has become more important with the advent of anti-CMV therapy.