Type I Helicobacter pylori strains frequently recognize the Lewisb (Leb) blood group antigen. This binding property and expression of the Leb oligosaccharide were required for adherence to fixed normal or pathologic gastric tissue. In contrast, both type I and type II strains adhered to cultured cells in the absence of the Leb epitope. For the gastric cell line AGS, adherence was significantly higher when viable type I strains were allowed to interact with viable AGS cells compared with fixed cells. The observation that chloramphenicol and cycloheximide, inhibitors of bacterial and eukaryotic protein synthesis, respectively, significantly reduced adherence of type I but not type II isolates suggests that in type I strains, adherence depends on the up-regulation of one or more host cell receptors triggered by the bacterium.