Experiments were designed to examine whether inhibition of the renin-angiotensin system alters gastric mucosal damage in conscious rats subjected to restraint. Two hours immobilization resulted in an ulcer index of 46 +/- 4 (n = 16) which was decreased by converting enzyme inhibitor (MK 422, enalaprilat) doses of 1 and 10 mg.kg-1.h-1 by 50 +/- 16 (n = 8) and 66 +/- 8% (n = 13), respectively (p < 0.05). Gastric blood flow measured by both the 99Tc-labelled frog erythrocytes and 86Rb-clearance methods was low in untreated rats and increased to more than three-fold in angiotensin converting enzyme inhibitor treated animals. Infusion of saralasin a specific angiotensin II receptor blocker (5 micrograms.kg-1.h-1, n = 25) also decreased the ulcer index by 40 +/- 5% (p < 0.05). Thus inhibition of the renin-angiotensin system in conscious cold-restraint rat increased gastric blood flow and reduced mucosal damage. These results suggest that the renin-angiotensin system plays a significant role in the development of experimental gastric ulcer in the cold-restraint model.