Macrolide resistance trends were examined among Helicobacter pylori strains from 154 patients between 1994 and 1998. Applicabilities of screening agar method (SAM) and modified disk diffusion method (MDDM) were evaluated. Overall primary resistance rates to erythromycin and clarithromycin were 14.8% and 8.7%, respectively. No association was found with age, sex, and diseases. Clarithromycin-resistance rate reached 12.5% in the last 2 years. Secondary resistance to erythromycin occurred more often (in 62.5%) than to clarithromycin (in 42.9%). Therapy with spiramycin or erythromycin in four cases induced no clarithromycin resistance. These data show a considerable prevalence of H. pylori resistance to macrolides, which exhibited a tendency to increase and was often associated with metronidazole resistance. By comparing the MDDM with SAM, an overall agreement was obtained in 81 (94.2%) of 86 results. MDDM and SAM are reliable techniques for testing H. pylori susceptibility to macrolides.