Among people infected with Helicobacter pylori, the virulence of the infecting strain is a major determinant of who develops disease. Strains producing vacuolating cytotoxin activity are more commonly isolated from people with peptic ulcers than without. The gene encoding the toxin, vacA, varies between strains, especially in its signal sequence and mid regions. vacA genotype influences cytotoxin activity, and signal sequence type correlates closely with peptic ulceration. Infection with strains possessing cagA (cytotoxin associated gene A) is more common among people with peptic ulceration or gastric adenocarcinoma than without. cagA is a marker for the cag pathogenicity island, which includes genes necessary for the enhanced inflammation induced by pathogenic strains. Serological detection of infection with cagA+ strains is at present the best practical test for virulence. However, before a strategy of screening and selective treatment can be considered, it is important to assess whether cagA- strains are entirely non-pathogenic.