The effects of lansoprazole given intravenously on indomethacin-induced gastric bleeding and mucosal lesions were investigated in rats in comparison with those of omeprazole, famotidine and ranitidine. Lansoprazole inhibited gastric bleeding induced by indomethacin with an ID50 value of 0.29 mg/kg. Omeprazole and famotidine significantly inhibited gastric bleeding, but ranitidine provided negligible inhibition. A correlation was found between the inhibitory action of lansoprazole on gastric bleeding, and acid secretion, and its inhibitory action on gastric bleeding was almost completely abolished by adding 50 mM-HCl to the gastric perfusate, suggesting that lansoprazole's inhibitory action on gastric bleeding was mainly due to its antisecretory action. Lansoprazole inhibited the development of gastric lesions induced by indomethacin with an ID50 value of 0.10 mg/kg, whereas histamine H2-receptor antagonists did not display a potent inhibitory effect. ID50 values for omeprazole, famotidine and ranitidine were 0.69, 2.58 and 24.6 mg/kg, respectively. These results indicate that lansoprazole has a potent inhibitory action on indomethacin-induced gastric bleeding and mucosal lesions and that it is useful in the treatment of acute gastric mucosal lesions.