Background & Aims: Molecular mimicry of Lewis blood group antigens by Helicobacter pylori may be involved in immune evasion by the bacteria and in the pathogenesis of chronic atrophic gastritis. Helicobacter mustelae infects ferrets naturally, causing gastritis, and may be involved in ulcerogenesis. The aim of this study was to determine if H. mustelae shows a similar form of molecular mimicry. Methods: Antibodies raised against H. mustelae were used to stain ferret gastric tissue by immunoblotting, immunohistochemistry, and flow cytometry. Epitopes recognized by cross-reactivity were characterized by proteinase K and sodium metaperiodate treatment. Results: H. mustelae antiserum reacted with H. mustelae and with ferret gastric tissue. Absorption of the antiserum with H. mustelae or ferret and rabbit gastric tissue removed the cross-reactive antibodies. Antibodies reacted with a blood group antigen A–like structure on ferret gastric epithelial cells and H. mustelae lipopolysaccharide. Conclusions: H. mustelae expresses a blood group–like antigen as part of its lipopolysaccharide that may be used as a method of immune evasion by mimicry of gastric epithelial cells. The cross-reactivity shown by H. mustelae–specific antibodies with gastric mucosa may suggest a role for autoantibodies in the pathogenesis of H. mustelae–induced gastritis in ferrets. GASTROENTEROLOGY 1998;114:690-696