A layer of water-insoluble mucus gel is secreted by the gastric epithelium, and is believed to form an important barrier to acid injury. It is postulated that Helicobacter pylori can alter pH gradients by damaging the mucus layer, but no data on pH gradients in vivo in patients with H. pylori gastritis have been published. We aimed to construct a map of mucus-bicarbonate layer pH gradients in health and disease. Fourteen healthy asymptomatic volunteers (mean age, 46 yr) and 14 symptomatic patients with non-ulcer dyspepsia (NUD) (mean age, 46 yr) were studied. A flexible pH microelectrode was passed through the biopsy channel of an endoscope; luminal readings and three mucosal surface pH readings were obtained from each of five specific gastric sites (fundus greater curve, body greater curve, antrum greater curve, antrum lesser curve, and antrum anterior wall) using standardized methodology. Gradients at each site were calculated (mean juxta mucosal pH minus luminal pH); pH electrode accuracy was tested in standard buffer solutions. Biopsies were obtained from each site to assess for H. pylori status. Among asymptomatic volunteers, 21% had H. pylori; in NUD, 50% were infected. There was a significant association between H. pylori and histological gastritis at each site. The overall mean (+/- SE) pH gradients in H. pylori-positive and -negative cases were similar, being 5.35 (+/- 0.06) and 5.26 (+/- 0.07), respectively. There was also no significant correlation between the histological gastritis score and the pH gradient at each gastric site. The pH gradients in healthy subjects (mean 5.31) and NUD (mean 5.29) were not significantly different. We conclude that pH gradients appear to remain stable throughout the stomach in healthy subjects and NUD, independent of H. pylori gastritis.