A liver transplant patient with previous episodes of diarrhea and pseudomembranous colitis due to Clostridium difficile subsequently developed pseudomembranous colitis due to cytomegalovirus. The patient responded to ganciclovir. Cytomegalovirus infection should be considered in the differential of pseudomembranous colitis in immunocompromised patients, particularly when C. difficile toxin assays or cultures are negative.