The bacterium Helicobacter pylori is the causative agent for peptic ulcer disease. Bacterial adherence to the human gastric epithelial lining is mediated by the fucosylated Lewis b (Le(b)) histo-blood group antigen. The Le(b)-binding adhesin, BabA, was purified by receptor activity-directed affinity tagging. The bacterial Le(b)-binding phenotype was associated with the presence of the cag pathogenicity island among clinical isolates of H. pylori. A vaccine strategy based on the BabA adhesin might serve as a means to target the virulent type I strains of H. pylori.