The effect of pentacaine on different models of gastric and duodenal damage and on gastric acid secretion was studied after oral and parenteral administration. A proportional involvement of local and systemic effects of pentacaine was found in phenylbutazone-induced and cold-restraint stress-induced lesions, whereas in ethanol- induced lesions oral administration was the only effective way. On the other hand, duodenal lesions and gastric acid secretion were substantially affected by parenteral administration. The possible mechanisms involved in these differences are discussed.