The aim of this study was to determine the range of activity and the location of lipase in the human stomach. The range of lipase activity in gastric mucosa of surgical specimens from the fundic area of 22 subjects was 594 to 3350 mU [mean, 1598 +/- 144 mU tri[3H]olein, (1 mU-1 nmol [3H]oleic acid released from tri[3H]olein per minute per milligram protein)]. For localization of activity, pinch biopsy specimens of gastric mucosa from 6 subjects were taken from the greater and lesser curvatures within 2 cm of the gastroesophageal junction (upper greater curvature and upper lesser curvature) and within 2 cm of the pylorus (lower greater curvature and lower lesser curvature). Lipase activity was higher in the upper greater curvature (405 +/- 92 mU) than in the upper lesser curvature (32 +/- 13 mU) and lowest in the antral area (16 +/- 9 mU in the lower lesser curvature and 10 +/- 2 mU in the lower greater curvature). The data show that in the human, lipase activity is localized primarily in the fundic area of the stomach. Comparison of the lipase activity levels in the gastric mucosa with lingual lipase activity levels in specimens of lingual serous glands indicates that in humans, gastric lipase is the main lipase active in the stomach.