Measurements of pH in the microclimate on gastric and duodenal mucosa were made during gastrointestinal endoscopy in 21 normal subjects and 9 duodenal ulcer patients. In controls luminal and juxtamucosal mean pH (+/- SEM) of 3.29 +/- 0.3 and 4.48 +/- 0.25 were recorded respectively in distal esophagus, 2.01 +/- 0.17 and 4.84 +/- 0.37 in gastric fundus, 1.82 +/- 0.12 and 5.5 +/- 0.15 in body, 3.52 +/- 0.34 and 5.42 +/- 0.29 in antrum, 6.89 +/- 0.21 and 7.16 +/- 0.13 in duodenal cap, and 6.84 +/- 0.19 and 7.03 +/- 0.19 in proximal duodenal loop. When the lumen of esophagus and duodenum were perfused with acid (pH 2) luminal and mucosal pH values were 2.18 +/- 0.11 and 4.08 +/- 0.41 in esophagus, 2.57 +/- 0.15 and 6.74 +/- 0.13 in duodenal bulb, and 2.44 +/- 0.14 and 6.39 +/- 0.2 in duodenal loop. Juxtamucosal pH in fundus, body, and duodenum remained near neutral when luminal pH was 1.5, but in distal esophagus and antrum it fell sharply at luminal pH values below 3. In duodenal ulcer patients juxtamucosal pH in the cap was significantly lower than that in normals at luminal pH values below 3. These studies support the hypothesis that a "mucus-bicarbonate" barrier inhibits mucosal acidification in humans and that duodenal mucosa in ulcer patients is less able to maintain a neutral zone adjacent to it in the face of luminal acid.