In 21 patients who had undergone total pancreatectomy for pancreatic head carcinoma, the uninvolved pancreas was examined with regard to the type, incidence and regional distribution of duct epithelial proliferation. The results were compared with those in 37 operative specimens from patients with chronic pancreatitis, in 46 normal pancreases from autopsies and with findings in experimental pancreatic carcinogenesis. While the incidence of squamous metaplasia and non-papillary epithelial hypertrophy varied little in the different groups, papillary epithelial hyperplasia was found three times more often in cases of carcinoma, with associated mild duct obstruction. Atypical epithelial proliferation was only detected in the vicinity of carcinomas. Unequivocal transition from papillary hyperplasia to atypical proliferation was not observed. In hamsters treated with dihydroxy-di-n-propylnitrosamine (DHPN) for induction of pancreatic duct carcinomas, the early duct lesions closely resembled atypical epithelial proliferation of human pancreas. It is concluded that (1) papillary epithelial hyperplasia is probably only indicative of early duct obstruction and/or a general neoplastic stimulus, (2) intraductal epithelial proliferation with atypia is a true precursor of duct carcinoma, and (3) chronic pancreatitis lacks atypical duct lesions.