1. Extracts of human stomach homogenized in Krebs solution had more PGE(2)-like activity than tissue homogenized in acid/ethanol or in the presence of indomethacin, indicating that the tissue can synthesize PGE(2).2. The distribution and synthesis of PGE(2)-like substance in human stomach was determined by extracting frozen sections cut parallel to the mucosal surface. Peak levels usually occurred at a depth of 0-600 mum in the mucosa.3. Small amounts of a PGE(2)-like substance were present in basal gastric juice, and its concentration was usually even lower in secretion stimulated by pentagastrin or histamine.4. Submaximal acid secretion produced by I.V. infusion of pentagastrin generally fell slightly when indomethacin was administered rectally to inhibit PG synthesis.5. These experiments, together with the findings that orally administered PGE compounds do not inhibit human gastric acid secretion, seem to argue against a possible inhibitory role for PGE(2) in gastric acid secretion in man.6. If this is so, it would follow that gastric bleeding caused by aspirin-like drugs is not due to increased acid secretion. A hypothesis is presented that tissue damage following vasoconstriction and ischaemia, due to inhibition of PG synthesis in blood vessels, contributes to the bleeding.