Teprenone (geranylgeranylacetone) is a gastric mucosal protective drug used clinically in Japan for treatment of gastric ulcers and gastritis. Its effect on portal hypertensive (PHT) gastric mucosa which has impaired defensive mechanisms is not known. In 20 PHT and 20 sham-operated rats, we studied the effects of teprenone or placebo on: (1) portal pressure; (2) gastric pH; (3) gastric mucosal blood flow using laser Doppler flowmetry, and (4) hexosamine content in gastric mucosa. The gastric mucosal blood flow was significantly higher in the PHT + teprenone group than in the PHT + placebo group (463 ± 75 and 381 ± 82 perfusion units, respectively; p < 0.05). The hexosamine content was significantly lower in PHT rats than in sham-operated controls (12.6 ± 2.3 vs. 14.3 ± 2.2 μg/mg, respectively). Teprenone treatment significantly increased the gastric mucosal hexosamine concentration in both sham-operated and PHT rats (17.2 ± 3.1 and 15.6 ± 3.6 μg/mg, respectively). These effects of teprenone, combined with its known prostaglandin-stimulat-ing action, suggest a potential role for this agent in the treatment of PHT gastric mucosal abnorm