Colloidal bismuth subcitrate (CBS, De-Nol®) heals duodenal ulcers but with a lower relapse rate than cimetidine, perhaps due to inhibition of Campylobacter pyloridis (CP) organisms. To test this hypothesis we studied gastric mucosal histology in three groups of ulcer patients treated with either cimetidine, CBS, or CBS in combination with an antibiotic. Cimetidine had no effect on CP or gastric mucosal histology but with CBS therapy there was a significant reduction in the number of bacteria (p < 0.0001). However, relapse of both CP infection and gastritis usually occurred once CBS was withdrawn. When CBS was combined with amoxycillin or tinidazole, long-term disappearance of both CP bacteria and gastritis was achieved (p < 0.0001). In ultrastructural studies 30–90 min after single oral doses of CBS or bismuth subsalicylate, CP had detached from the gastric epithelial cells and exhibited structural degradation associated with the selective deposition of a paniculate bismuth complex within and upon the surface of the organisms. In vitro, CP and other campylobacters were inhibited by bismuth compounds at 25 mg/l but they were resistant to cimetidine and ranitidine. CBS has a powerful antibacterial effect against CP but relapse of infection is common after CBS alone. In combination with antibiotics however, eradication of CP and long-term healing of gastritis occurs. In such cases the gastroduodenal mucosa is intact, and less likely to ulcerate.