Helicobacter pylori is associated with development of gastritis, gastric ulcers, and adenocarcinomas in humans. The Lewis(b) (Le(b)) blood group antigen mediates H. pylori attachment to human gastric mucosa. Soluble glycoproteins presenting the Leb antigen or antibodies to the Leb antigen inhibited bacterial binding. Gastric tissue lacking Leb expression did not bind H. pylori. Bacteria did not bind to Leb antigen substituted with a terminal GalNAc alpha 1-3 residue (blood group A determinant), suggesting that the availability of H. pylori receptors might be reduced in individuals of blood group A and B phenotypes, as compared with blood group O individuals.