Duodenal disease resulting from cytomegalovirus (CMV) infection is unusual in the absence of other gastrointestinal disease. We report two cases of CMV infection symptomatically isolated to the duodenum. One patient presented with ulcer-type dyspepsia, and the other with severe gastrointestinal bleeding. Ganciclovir therapy resulted in both a clinical and endoscopic remission. The importance of endoscopic evaluation is discussed given the necessity of mucosal biopsy for diagnosis and the availability of specific and effective therapy. © 1992 Raven Press, Ltd., New York.