Abstract: Among more than ten isozymes of the carbonic anhydrase (CA) family, only cytoplasmic CA II and membrane‐bound CA IX have been reported to be expressed in human pancreas. To study the mRNA expression of CA isozymes in human pancreas, reverse transcriptase‐polymerase chain reaction (RT‐PCR)‐Southern blot analysis and cDNA sequencing following RT‐PCR were employed. CA II, IV, VI, IX, and XII were clearly identified in polyA+ RNA from normal human pancreas by RT‐PCR‐Southern blotting. Results with cultured pancreatic tumor cell lines suggest that CA II, IV, IX, and XII are expressed in the ductal cells, and CA VI is expressed in the acinar cells. We propose a hypothesis for the pathophysiological function of CA isozymes in human pancreas; (1) the intraluminal CA isozymes (CA IV, VI, and possibly XII) form a mutually complementary system with cytoplasmic CA II to regulate the luminal pH of the pancreatic duct system and work as a self‐defense mechanism against pancreatitis; (2) CA II and other CA isozymes play a pathological role in the autoimmune process of idiopathic chronic pancreatitis.