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BACKGROUND: Cystic fibrosis (CF) is characterized by pancreatic destruction following the gradual obstruction of small pancreatic ducts, from the mid-trimester of gestation onwards. To date, the material causing the obstruction has not been identified. The MUC6 mucin cDNA was isolated from human stomach and has been shown to be expressed in a number of other tissues in the gastrointestinal tract, including the gall bladder and parts of the ileum and colon. MATERIALS AND METHODS: We have examined the expression of MUC6 mucin in the human pancreas, both during development and postnatally, by mRNA in situ hybridization and immunocytochemistry. RESULTS: In this report we establish that MUC6 transcripts are abundant in pancreatic epithelial cells and show a very similar pattern of expression in the epithelium lining small ducts and centroacinar cells to that shown by the cystic fibrosis transmembrane conductance regulator gene (CFTR). In addition, material obstructing the pancreatic ducts of CF pancreas was shown to contain MUC6 mucin. CONCLUSION: We have identified MUC6 mucin as a significant constituent of the material obstructing the small pancreatic ducts in CF.