Background: Strategies to improve antibiotic treatment of Helicobacter pylori infection are hampered by lack of knowledge about the route of antibiotic delivery. Post-prandial dosing with antibiotics prolongs their gastric residence time and improves their intragastric distribution, leading to improved local delivery compared with pre-prandial dosing. We aimed to assess whether pre- or post-prandial dosing with amoxycillin suspension was more effective for H. pylori eradication in an amoxycillin/omeprazole regimen. Methods: Seventy-nine patients with H. pylori infection were treated with omeprazole 40 mg o.m. for 28 days and amoxycillin suspension 500 mg q.d.s. for days 15-28, the amoxycillin being randomized to either 1 h before or immediately after food. Results: The H. pylori eradication rate, for those completing the trial, was 67% (22/33) when amoxycillin suspension was given pre-prandially, compared with 39% (15/38) when it was given postprandially (P < 0.05). Good compliance was achieved, with H. pylori eradication in 59% (28/46) of good compliers compared with 36% (9/25) of others completing the protocol (P < 0.05). Conclusion: When given with omeprazole, pre-prandial dosing with amoxycillin suspension is more effective for H. pylori eradication than post-prandial dosing. This is consistent with the hypothesis that systemic rather than local delivery of amoxycillin is important for H. pylori eradication.