The etiology of gastric pain is an unsolved riddle, despite nearly a century of research. While much research and many pharmacologic treatment methods have been aimed at controlling acid secretion, the role of acid in reports of pain is unclear. In this study, 30 patients (10 with endoscopically verified duodenal ulcers, 10 with verified nonulcer dyspepsia, and 10 healthy volunteers) participated in a double-blind crossover study of the effects of ranitidine on pain reports after an injection of pentagastrin. The results showed that whereas pentagastrin caused a significant increase in gastric secretion, only the patients with nonulcer dyspepsia reported any appreciable pain before or after the injection. In addition, they chose more adjectives to describe their pain and reported more symptoms, especially directly after the injection. There were no significant differences between the drug and placebo conditions nor between the ulcer and healthy subjects. The role of acid in reported pain remains unclear.