It has previously been reported that acemetacin, a carboxymethyl ester of indomethacin, is converted to indomethacin almost completely by in vivo enzymatic attack, and thus its pharmacological effects are considered to be derived from its active metabolite, indomethacin. Gastric erosions of a slight degree were observed after a single oral administration of acemetacin, whereas indomethacin induced very severe gastric erosions 3 to 5 hours after dosing. On the other hand, the degree of intestinal lesions induced by acemetacin which became apparent 24 hours after dosing were about the same as that induced by indomethacin. The same results were obtained following repeated administration of the drugs. In an in vitro study, indomethacin was found to cause a significant mucosal loss of the isolated rat's small intestine, while there were no changes observed in case of an acemetacin treatment. Indomethacin also markedly inhibited the prostaglandin formation in the gastric mucosa of the rat treated with a single oral dose of the drug. In this test, the inhibitory effect of acemetacin on prostaglandin formation was found to be about half as potent as that of indomethacin. From these data, the less gastric damaging effects of acemetacin as compared to indomethacin can be explained by the fact that acemetacin does not have direct irritative effects on the mucous membrane. Furthermore, it could be due in part to the different abilities of these two drugs to inhibit prostaglandin formation in the gastric mucosa.