To elucidate the mechanism of the anti-ulcer effect of rebamipide (2-(4-chlorobenzoylamino)-3-[2-(1H)-quinolinon-4-yl] propionic acid), changes in glycosaminoglycan (GAG), uronic acid and hexosamine contents of stomach tissue were examined in rats treated with the ulcer-inducing agents and/or rebamipide. Uronic acid and hexosamine contents in acid hydrolysates of stomach tissue were increased after diethyldithiocarbamate (DDC, 800 mg/kg, s.c.) or histamine (300 mg/kg, i.p.) treatment, and similar changes in the GAG, uronic acid, and hexosamine levels were observed in stomach tissue extracts. Pretreatment with rebamipide (60 mg/kg, i.p.) resulted in an additional increase in the contents of the above components after DDC or histamine treatment. However, rebamipide treatment alone did not increase the gastric contents of GAG and GAG components in normal rats. Gel filtration chromatography of extracted GAGs suggested that DDC, histamine and rebamipide treatments do not cause a change in the aggregated forms of gastric GAGs. These results suggest that rebamipide stimulates the GAG synthesis in the ulcerated stomach and that this effect may contribute to the healing process of gastric ulcer.