The distribution of prostacyclin-(PGI2-)sensitive adenylate cyclase in human gastric and duodenal mucosa was studied. Like PGE2, PGI2 induced a dose-dependent increase of enzyme activity throughout the stomach and the duodenum. Maximal effects (about 2.5- to 3.0-fold increase) were observed at a PGI2 concentration of 0.28 mmol/l. The stable breakdown product 6-keto-prostaglandin F1α (6-keto-PGF1α) was much less active. The equal distribution of the PGI2-sensitive adenylate cyclase in the human upper alimentary tract suggests a localization of this enzyme system in cells not directly related to gastric acid secretion.