Helicobacter pylori infection has been implicated in the development of chronic active gastritis and gastric neoplasms (ie, mucosa-associated lymphoid tumors and adenocarcinoma). The potential association between esophageal H pylori infection with Barrett's esophagus-associated adenocarcinoma has not been previously studied. Nineteen cases of adenocarcinoma arising in Barrett's esophagus were examined for the presence of H pylori. Barrett's esophagus was defined by the presence of metaplastic specialized-type epithelium (gastric-type epithelium with goblet cell metaplasia) in the distal esophagus. To detect the presence of H pylori, 5-microm sections, from several tissue blocks in each case, were stained with routine hematoxylin-eosin, modified Giemsa, and an antibody directed against H pylori (Dako a/s, Denmark, Lot # 111061). Stained sections were examined independently by two pathologists. All three staining methods failed to show H pylori in any of the cases examined. Sections of Barrett's esophagus (with and without dysplasia), adenocarcinoma, and stomach (when available) were uniformly negative for the presence of H pylori. We conclude that neither gastric nor esophageal infection with H pylori is a requisite for the development of adenocarcinoma in Barrett's esophagus. Moreover, it is unlikely that a significant association between H pylori infection and Barrett's-associated adenocarcinoma exists.