Helicobacter pylori strain diversity was investigated in infected persons by collection of multiple biopsies before and after therapy failure. It was demonstrated by random amplification of polymorphic DNA polymerase chain reaction that patients may be infected with a mixed population of H. pylori strains. Most patients were colonized with a predominant strain accompanied by up to 5 variant strains. The use of antimicrobials resulted in an altered distribution of the strains present, but the predominant strain usually remained. Patients may be infected with a mixed population of metronidazole-sensitive and -resistant strains at one time, with metronidazole-based therapy selectively enriching for a resistant population.