Esterase, aminopeptidase, carboxypeptidase, and endopeptidase activities were quantitated in homogenates of rat and hamster buccal and intestinal tissues. Whole homogenates (cytosol + cell membranes) of both tissues from the rat had higher esterase activity than supernatants of these homogenates. In both species intestinal homogenates showed significantly higher esterase and amino-peptidase activities than buccal homogenates, while carboxypeptidase activity in buccal homogenates was significantly higher than intestinal homogenates. Although hamster buccal and intestinal homogenates had similar levels of endopeptidase activity, rat intestinal homogenates had significantly higher endopeptidase activity than buccal homogenates. The results suggest that the utility of the buccal mucosa as a delivery route for some drugs may be compromised - as with the intestinal mucosa - by the presence of drug-degrading enzymes in the mucosa.