Analysis of 32 Helicobacter pylori strains indicated a strong association between the presence of the cagA gene and a specific type of vacA allele found predominantly in cytotoxin-producing strains (P < .001). To determine whether tox+/CagA+ and tox-/CagA- strains constituted two separate noncombining lineages, sequences of the H. pylori ureC gene, cysS homologue, and the intergenic region between cysS and vacA were determined for multiple strains. The mean levels of nucleotide identity in the three regions were 96.7% +/- 0.5%, 95.0% +/- 1.0%, and 89.0% +/- 2.9%, respectively. Multiple sequence alignments and dendrograms based on these three regions failed to identify two clonal populations of organisms for which cagA and vacA genotypes were markers. The presence of a 63- to 64-bp insertion in the cysS-vacA intergenic region was unrelated to the vacA genotype of the strains. These data suggest that recombination between Helicobacter genomes may occur in vivo.