The ulcerogenic actions of aspirin and sodium salicylate in cat gastric antrum following intravenous injection, and their effects on the synthesis of two major cyclo-oxygenase products by antral mucosa have been determined. Near-maximal rates of gastric acid secretion were stimulated by histamine, infused i.v. for 1 h prior to bolus injection of aspirin or salicylate and throughout the subsequent 4 h. The area of lesions in the cat gastric antrum were then assessed macroscopically and the generation of both 6-oxo-PGF1 alpha and PGE2 from strips of antral mucosal tissue following 1 min vortex-incubation was determined by radioimmunoassay. The plasma and mucosal-tissue levels of both aspirin and salicylate were determined using HPLC techniques. Aspirin (0.2 mmol. kg-1 i.v.) induced substantial deep antral ulceration during the 4 h histamine infusion, whereas sodium salicylate (0.2 mmol. kg-1 i.v.) caused no significant macroscopic damage. Sodium salicylate likewise caused no significant inhibition in the ex vivo generation of either 6-oxo-PGF1 alpha or PGE2, whereas aspirin induced 92 +/- 3 and 97 +/- 1% inhibition of generation of these prostanoids respectively. The levels of total salicylate in plasma and mucosal tissue were comparable following bolus i.v. injection of aspirin or sodium salicylate. These observations support the concept that cyclo-oxygenase inhibition is an important mechanism underlying deep gastric ulceration induced by aspirin, when administered parenterally in the cat.