This is a retrospective study of 54 consecutive upper gastrointestinal endoscopies in marrow graft recipients performed to determine the incidence and distribution of CMV infection in symptomatic patients and to compare the sensitivities of 7 CMV detection techniques. At each endoscopy, 3 biopsies were obtained from the esophagus, stomach, and duodenum. Each of the 3 biopsies was assayed for CMV by different techniques. Enteric CMV was identified by one or more techniques in 52 of 486 (11%) biopsies from 14 infected patients. All patients infected with CMV initially had nausea and vomiting. In 13 of these patients, there was esophageal CMV, often associated with stomach (10 patients) and duodenal (7 patients) involvement. CMV infection of the esophagus was never identified cytologically in esophageal imprints or histologically, immunohistologically, or by DNA hybridization in esophageal epithelial cells. The most sensitive diagnostic methods were conventional and centrifugation cultures, which each identified CMV in 17 of the 30 (57%) organs positive by any technique. Indirect fluorescent antibody (IFA) staining for a late CMV antigen detected 53%, followed by in situ DNA hybridization (40%), IFA and immunoperoxidase (IP) staining for an early CMV antigen (37% and 43%), and routine histology (30%). Although no single detection technique is completely adequate for the rapid identification of CMV in small endoscopic biopsies, centrifugation culture is the method of choice, with supplementary immunohistology and in situ hybridization of archival tissue if needed.