Cytoplasmic carbonic anhydrase (CA) II is involved in acid-base balance in a wide variety of tissues. Extracellular CAs, membrane-bound CA IV and excretory CA VI, play a cooperative role with CA II in regulating the luminal pH in kidney and salivary glands, respectively. To extend the evidence into pancreas, we studied messenger RNA (mRNA) expressions of CA IV and CA VI in human pancreas. mRNA expressions of CA II, IV, and VI were studied in human pancreas, kidney, liver, and salivary glands by three different detection methods: reverse transcription-polymerase chain reaction (RT-PCR), RT-PCR-Southern blot, and Northern blot analyses. CA IV mRNA expression was consistently detected in all four tissues except for liver; only RT-PCR-Southern blot successfully identified its expression in liver. In contrast, RT-PCR and RT-PCR-Southern blot identified CA VI mRNA in salivary glands and pancreas, but Northern blot failed to detect its expression in pancreas. There was no detectable signal of CA VI expression in kidney and liver by all detection methods. CA II mRNA expression was consistently detected in all tissues studied. These results indicate that pancreas and salivary glands contain both of CA IV and VI and suggest that the extracellular CA isozymes may form a mutually complementary system with CA II to regulate the luminal pH of the pancreatic duct system.