Carbonic anhydrase (EC 188.8.131.52) was detected histochemically from the following regions in patients of various ages (14-84 yr): buccal mucosa, buccal flap, hard palate and tongue. The enzyme was principally located in the cell membranes but was also present in nuclei. There was a gradation in activity from basal (strong) to superficial cells (weak/negative). The carbonic anhydrase inhibitors ethoxyzolamide and acetazolamide abolished activity at 0.001 mM, but were ineffective, even at 1.2 mM, against a reaction associated with the granules of the stratum granulosum. No activity was detected in the absence of bicarbonate from the substrate.