It has been suggested that the putative Helicobacter pylori virulence factor hrgA is the first disease-specific marker for an H. pylori-related disease, (i.e., development of gastric cancer in East Asia). Our aim was to test the hypothesis that the presence of hrgA has disease specificity. We examined 458 H. pylori isolates including 289 from East Asia and 169 from Western countries whose cagA and vacA genotypes had previously been characterized. hrgA/hpyIIIR status and iceA genotypes were determined by polymerase chain reaction using DNA expanded from a single colony. hrgA was present in 29% of gastric cancers, 29% of ulcers, and 31% of gastritis cases among H. pylori from East Asia (P > 0.9). Overall, there was no significant relationship between the presence of the hrgA gene and disease presentation (cancer, ulcer, or neither) or between its presence and the cag pathogenicity island, vacA s1 , babA2, and oipA, "on" genotypes. The prevalence of the hrgA gene was significantly lower in H. pylori from East Asia (29%) vs. those from the West (49%) (P < 0.001). The prevalence of the hrgA gene was not related to clinical outcome or to other important putative virulence factors.