We report a case of toxic megacolon manifesting in cytomegalovirus (CMV) colitis in a 55-yr-old man with steroid-dependent chronic obstructive pulmonary disease. He presented to the hospital with increasing dyspnea and low-grade fever. His hospital course was characterized by the poor response of his symptoms to treatment, and by the subsequent development of intermittent hematochezia and, eventually, acute abdomen. The surgical specimen showed dilatation of the cecum and ascending colon with a solitary mucosal ulcer in the latter. The major histologic changes were limited to the area of ulceration. In addition to classical CMV inclusions. vasculitis manifested in two forms, namely, leukocytoclastic type and fibrinoid necrosis. The patient died shortly thereafter, due to multi-organ system failure. To our knowledge, this represents the first reported case of toxic megacolon due to CMV infection without underlying inflammatory bowel disease. The pathogenesis of toxic colonic dilatation remains unknown.