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Recommended therapies with the highest eradication rates for Helicobacter pylori (HP) are triple therapies comprising bismuth salts, nitroimidazole and amoxicillin or tetracycline. Primary and secondary resistance of HP to nitroimidazole, however, represents a major problem of this treatment since it is the main cause of eradication failure. In these cases therapeutic regimes without nitroimidazole could prove more successful. High dose omeprazole/amoxicillin has been suggested as a simple and effective therapy with few side effects. The effectiveness of this combination in eradicating metronidazole resistant HP has not been established so far. The aim of this study was to evaluate high dose omeprazole/amoxicillin in eradicating metronidazole resistant HP in our population. 33 patients (6 women, 27 men, mean age 39 [range 21-68]) with recurrent duodenal ulcer and gastric colonization by metronidazole resistant HP were examined. Smokers were defined as patients currently smoking > 10 cigarettes/day. Exclusion criteria were: gastric surgery or intake of antibiotics, omeprazole bismuth salts and NSAIDs within four weeks before study entry endoscopy. Biopsy specimens were obtained in a standardized manner: 5 from the gastric antrum (1 CLO, 1 culture, 3 histology: H & E, Giemsa) and 2 from the gastric body (histology). Resistance testing for penicillin, amoxicillin and metronidazole was performed using a disk diffusion test (E-test, AB Biodisk, Sweden). Metronidazole resistance was defined as a minimal inhibitory concentration (MIC) of metronidazole of > 8 micrograms/ml. Eradication therapy consisted of oral omeprazole (40 mg bid) and amoxicillin solute (750 mg tid) for 10 days. Subsequently, for ulcer treatment, patients were given omeprazole (20 mg per day) for 20 days.(ABSTRACT TRUNCATED AT 250 WORDS)