Carbonic anhydrases (CAs) catalyze the hydration and dehydration of carbon dioxide. They are important for regulating ions, fluid and acid-base balance in many tissues. The location of CAs by cell type is important for understanding their roles in these functions. CAs II and VI have been demonstrated using immunohistochemistry (IHC) in the serous acinar cells of human salivary glands and ducts of rat salivary glands. CA IV has been localized by IHC to the ducts of rat salivary glands. CA IV also is present in human parotid glands as shown by real time-polymerase chain reaction (RT-PCR), but this method does not show the distribution of the CA isozymes by cell type. We investigated the cell-specific distribution of CA IV in the human parotid gland. Sections from five formalin fixed, paraffin embedded specimens of human parotid gland were subjected to IHC for CA IV using a commercial antibody. Moderate to strong reactions were found in the cell membranes and cytoplasm of the intercalated, striated and excretory ducts and capillaries, and reactions in the acini were limited to faint areas in some cells. These results indicate that CA IV participates in the regulation of bicarbonate/carbon dioxide fluxes in the ductal system of the human parotid gland.