Helicobacter pylori isolates from 18 patients were examined by macrorestriction DNA analysis to determine whether > or = 2 strains can coexist in the human stomach. Four biopsy samples from different sites in each patient's stomach were cultured, and 12-14 clones of H. pylori per patient were analyzed. DNA of 15 of the 18 isolates was digestible: 12 by NotI and 3 by NruI. Within 14 of these digestible isolates, the patterns of all clones were identical. The isolate of 1 patient showed two digestion patterns, a finding that was confirmed by arbitrary primer polymerase chain reaction. The typeable isolates of all patients, except 2 who underwent gastroscopy on the same day, differed markedly from each other. These results indicate a noticeable discrepancy between the pronounced interpatient heterogeneity and the rare intrapatient variation of H. pylori.