The efficacy of high dose omeprazole/amoxicillin (OME/AMOX) for eradication of Helicobacter pylori (HP) is controversial. Reported eradication rates range from 0% to 90%. Different therapy schedules and unknown factors may be crucial; in particular, pretreatment with OME has been thought to endanger HP eradication by subsequent OME/AMOX. Preliminary findings suggested that smoking may impair eradication with OME/AMOX. The aims of this study were (1) to establish whether HP eradication rates differ depending on whether eradication with OME/AMOX was performed before or after ulcer therapy with OME, (2) to determine whether smoking impairs HP eradication by OME/AMOX and (3) to evaluate the efficacy of OME/AMOX in our population. 52 HP positive outpatients with endoscopically documented recurrent duodenal ulcer were included. Exclusion criteria were: alcoholism, previous gastric surgery, or intake of antibiotics, OME, bismuth salts, corticosteroids and NSAIDs within four weeks before study entry. Patients currently smoking > 10 cigarettes/day were classified as smokers. HP infection was confirmed by histology (3 biopsy specimens from the gastric antrum and 2 from the gastric body; H&E, Giemsa) and at least positive rapid urease test (CLO) or culture. Eradication therapy consisted of oral OME (40 mg bid) and AMOX solute (750 mg tid) for 10 days (OME/AMOX). This therapy preceded (group A) or followed (group B) ulcer therapy with OME (20 mg per day for 20 days). In group A 17 patients (2 females, 15 males, mean age 39 [19-70]; 11 smokers, 6 nonsmokers) underwent ulcer therapy with OME (d 1-20) before OME/AMOX d 21-30).(ABSTRACT TRUNCATED AT 250 WORDS)