OBJECTIVE To determine whether there has been a change in the patterns of susceptibility to various antibiotics of our isolates of Helicobacter pylori over a 5-year period from 1996 to 2000. METHODS Five hundred and fourteen isolates of H. pylori grown from gastric biopsies were tested for susceptibility to amoxycillin, clarithromycin, metronidazole and tetracycline. The usage of macrolide antibiotics in Australia was examined by calculating the numbers of prescriptions issued under the Australian pharmaceutical benefits scheme between 1992 and 2000. RESULTS There were no changes in susceptibility of H. pylori to amoxycillin and tetracycline and there was a slight decline in resistance to metronidazole. In contrast, there was a stepwise 4-fold increase from 3.8 to 15.7% in the number of isolates resistant to clarithromycin and a similar increase in the mean minimum inhibitory concentration of clarithromycin during the 5-year period of observation. There was no change in overall macrolide consumption in Australia over this and the preceding 3 years. However, the pattern changed, with erythromycin usage being halved and being replaced by roxithromycin and clarithromycin. CONCLUSIONS Resistance of H. pylori to clarithromycin is increasing, possibly as a consequence of increased usage of roxithromycin and clarithromycin. More patients are likely to fail to respond to empirical therapy and will need microbiological investigation.