Barrett’s esophagus and adenocarcinoma of the esophagus (5). Thus, from clinical and epidemiological studies, the pathogenetic significance of H. pylori is mixed. Both illness and protection from illness occur in only a small fraction of those carrying H. pylori, whereas for most carriers, morbidity and mortality are unaffected by their H. pylori status. In that sense, H. pylori can be considered a type of commensal, or more properly, has an “amphibiotic” relationship with humans (as with Bacteroides species), whose pathogenic significance is determined by context (6). Differences in the consequences of colonization could depend on variation among colonizing H. pylori strains, on environmental cofactors, or on factors determined by the individual host. In particular, DNA-level analyses have indicated that H. pylori is one of the most genetically diverse of bacterial species (3, 7, 8). Although much of the diversity may be neutral, some will affect the ability of these bacteria to colonize, persist, and/or affect disease in particular hosts. We aim to assess how H. pylori DNA sequence diversity (polymorphism) may affect disease risk in the broader context of signaling between microbes and hosts.