Geographical differences in the genetic diversity of Helicobacter pylori isolates were examined by analyzing rpoB sequences. An extremely high level of allelic diversity among H. pylori strains was found. The rpoB sequences of Asian and non-Asian (North and South American, European, and South African) strains were found to differ. An amino acid polymorphism (alanine and threonine RpoB types) was found at the 497th residue by deduced amino acid analysis. RpoB with a threonine residue (RpoB(Thr)) was uniquely present in East Asian countries, and two-thirds of the H. pylori isolate population in this region was RpoB(Thr); however, this type was rare or absent in Western countries, where RpoB(Ala) predominated. RpoB(Thr) strains induced a much larger amount of interleukin-8, a chemokine that plays an important role in chronic inflammation, than RpoB(Ala) strains in cultured MKN45 cells.