BACKGROUND Bismuth has been used as symptomatic treatment of dyspepsia for many years. It promotes healing of peptic ulcers and reduces their recurrence. The beneficial effect of bismuth on duodenal ulcer disease is thought to be due to an effect on Helicobacter pylori, although it has a rather weak bactericidal effect on H. pylori in vitro. Eradication of H. pylori in duodenal ulcer patients by a combination of bismuth, tetracycline and metronidazole has been reported to increase the density of somatostatin-producing D cells in the antrum. A reduced D cell density in the antral mucosa of duodenal ulcer patients could explain their exaggerated gastrin release. OBJECTIVE To test the possibility that bismuth could affect the neuroendocrine cells independently of the presence of H. pylori or not, we gave rats a diluted tripotassium dicitrato bismuthate solution by gastric gavage for 14 days. RESULTS Tripotassium dicitrato bismuthate treatment did not affect maximal pentagastrin-stimulated acid secretion or histamine release in isolated rat stomachs or the density of argyrophil cells in the oxyntic and antral mucosa. However, it significantly reduced the duodenal concentration of gastrin and calcitonin gene-related peptide, and the density of G cells in the antrum and duodenum. CONCLUSIONS The effect of tripotassium dicitrato bismuthate on the G cell may be of significance for its beneficial effect on duodenal ulcer disease.