In a previous study, the recurrence of the Campylobacter pylori infection after apparently successful antibacterial therapy was determined to be due to recrudescence rather than reinfection. Although the DNA patterns of pre- and posttreatment isolates were very similar, we detected minor differences between the two patterns in about one third of the patients. These differences were not artifacts, but originated in the coexistence in the stomach of (sub)populations of bacteria with slightly different chromosomal DNAs, plasmids, or both. The presence of such (sub)populations was probably caused by mutation in vivo, as mutation in vitro was demonstrated in one patient after the original isolate was subcultured 10 times. Minor differences were not correlated with a difference in susceptibility to the antibiotic(s) that was used. An additional conclusion of this investigation was that the results of plasmid analysis should be interpreted very carefully when this method is used as an epidemiologic marker in the investigation of C. pylori infections.