Nonulcer dyspepsia is a common clinical syndrome whose etiology is unknown. The sensitivity of the gastric mucosa to acid and duodenal contents in 18 patients with nonulcer dyspepsia was studied. The patients had a normal upper gastrointestinal endoscopy and biopsy specimens were obtained for determination of Helicobacter pylori status. Fifteen of the 18 patients were infected with H. pylori. All patients underwent intubation with double-lumen tube and collection of cholecystokinin-stimulated pancretico-biliary secretions. Subsequently, normal saline, 0.1N hydrochloric acid, and autologous duodenal secretions were infused into the stomach in a randomized blinded fashion. A positive response was defined as the production of epigastric pain by acid and/or bile but not by saline. By this definition, only 6 patients (33%) had a positive response and none had reproduction of their usual symptoms. In patients with a negative response, only 4 remained asymptomatic during all infusions. The remaining 8 had symptoms during infusion of saline, 7 of whom also had symptoms during infusion of acid and/or duodenal secretions. Two of these patients had reproduction of their usual symptoms. In conclusion, the gastric mucosa in patients with nonulcer dyspepsia is not abnormally sensitive to acid or duodenal contents.