Helicobacter pylori-associated gastritis is present in virtually all patients with duodenal ulcer (DU). Eradication of H pylori is associated with a highly significant decline in the recurrence rates of DU, indicating that treatments aimed at eradicating H pylori are mandatory in these patients. The novel proton pump inhibitor lansoprazole exhibits a potent antiulcer effect and, in vitro, a direct antibacterial effect against H pylori. Conflicting data have been reported on the question of whether lansoprazole is bactericidal against H pylori in vivo when administered alone. The aim of this double-blind trial was to address this issue further by comparing the effects of two different 4-week regimens (lansoprazole alone or in combination with amoxicillin) on H pylori infection in patients with DU. Patients were assessed before and after the 4-week treatment and 3 months after stopping the study medication. The ulcer healing rates at 4 weeks were similar for the two treatments while there was a trend for higher recurrence rates at 4 months in patients receiving lansoprazole alone. The frequency of high-grade H pylori infection was significantly lower in the lansoprazole and amoxicillin group both at 4 weeks (84% clearing) and 4 months. After 4 weeks of treatment there were no patients with residual H pylori-positive active antral gastritis in the lansoprazole and amoxicillin group compared with 25% in the lansoprazole alone group. Neither treatment significantly affected the IgG antibody response to H pylori either at the circulatory or the mucosal level. In contrast, the mucosal H pylori-specific IgA response was significantly enhanced after 4 weeks and more markedly after treatment with lansoprazole.(ABSTRACT TRUNCATED AT 250 WORDS)