Symptomatic patients (n = 101) with Helicobacter pylori infection were enrolled into a double-blind, double-dummy study to assess the efficacy of lansoprazole plus amoxycillin in the treatment of H. pylori infection. Patients were randomized to either lansoprazole 30 mg once daily (days 0-28) together with placebo (matched to amoxycillin) three times a day (days 0-14) followed by either placebo or amoxycillin 500 mg three times daily (days 15-28). Biopsy specimens for culture and histology were collected on days 0 and 56 or upon symptomatic relapse. Blood for serology was collected at days 0, 56 and 168. A [14C]-urea breath test was performed on day 168. Eighty-one (80.2%) patients completed the 56 day assessment. Of patients treated with lansoprazole plus amoxycillin, 35.1% (13/37) were cured of infection as assessed at day 56 (26.5% on an intention-to-treat basis), compared with 4.8% (2/42) of the placebo group (4% on an intention-to-treat basis). Recrudescence/re-infection occurred in one patient upon re-evaluation at day 168. Analysis of prognostic factors indicated that smoking and alcohol intake had little impact on the treatment outcome. Inflammation (both acute and chronic) improved in patients treated with lansoprazole plus amoxycillin. The relatively low efficacy of the treatment may relate to a single daily dose of lansoprazole (30 mg) being prescribed, treatment with amoxycillin being commenced 2 weeks after the initiation of lansoprazole or accurate assessment of treatment efficacy (both antral and body biopsy specimens taken).