In vitro and in vivo studies from various groups have suggested that Helicobacter pylori lipopolysaccharide (LPS) Lewis x (Le(x)) antigens mediate bacterial adhesion. We have now reevaluated this hypothesis by studying the adherence in situ of H. pylori strain 11637 and its corresponding Le(x)-negative rfbM mutant to human gastric mucosa from patients (n = 22) with various gastric pathologies. Significant binding of the parent strain was observed in only 8 out of 22 sections; in four out of eight patients, the Le(x)-negative mutant bound less well. One of these four patients displayed no gastric abnormalities, and the other three showed dysplasia, metaplasia, and adenocarcinoma, respectively; hence, we are unable to define the circumstances under which LPS-mediated adhesion takes place. We conclude that H. pylori LPS plays a distinct but minor role in adhesion.