Cytomegalovirus infection is one of the most prevalent viral infections affecting recipients of cardiac allografts. Of the various severe systemic manifestations, those in the gastrointestinal tract have a unique way of presenting, specifically in the colon where a process related to cytomegalovirus infection that involves all layers, with dilatation as a prominent clinical feature, has been suggested. We report herein a case of patient with a heart allograft who had severe episodes of rejection that responded to boosting doses of steroids. Because of persistent fever, diarrhea, hematochezia, and computed tomographic findings of the abdomen that showed a highly abnormal appearance of the ascending and transverse segments of the colon, this patient subsequently underwent celiotomy. The involved segment of the colon was found to have severe inflammation with mucosal necrosis; a subtotal colectomy was done. The abundant cytomegalovirus inclusions found in the vascular endothelium of the removed damaged segment of the colon suggest that cytomegalovirus may have been a causal factor in this form of colitis. The patient recovered uneventfully.