This study was performed to determine whether pancreatic parenchymal epithelial cells in human chronic pancreatitis tissues retain a biologically significant capability to proliferate and, if so, within which epithelial compartment proliferation occurs. The techniques of immediate per-operative in vitro labelling with bromodeoxyuridine (BrdU) and conventional immunohistochemistry for Ki-67 antigen expression were used to identify proliferating cells. Concordance between the two techniques was confirmed in all tissues examined. In normal pancreas, proliferation was restricted to acinar epithelial cells, with no activity in the ductules. In chronic pancreatitis of both chronic obstructive and chronic calcifying types, the number of proliferating cells in the acini was significantly increased. A small population of proliferating cells was also apparent within ductules in chronic calcifying pancreatitis, but not in chronic obstructive pancreatitis. This investigation has shown that loss of parenchymal epithelium occurring in chronic pancreatitis is not caused by a primary failure of pancreatic 'stem-cell' proliferation, but is due to disproportionate attrition of differentiated parenchymal epithelial cells by a mechanism, possibly stromal in origin, which remains hitherto unidentified. The presence of proliferating ductular cells in chronic calcifying pancreatitis, but not chronic obstructive pancreatitis, suggests that distinct pathogenic processes may be operating in the former condition, which is classically regarded as secondary to ductal obstruction by stones, and in this single respect might be considered to be identical to chronic obstructive pancreatitis. Preservation of 'stem-cell' function supports the belief that regeneration of pancreatic parenchymal tissue could be a feasible proposition if biologically appropriate management strategies were developed to treat chronic calcifying pancreatitis.