Non-neoplastic nodular lesions of the pancreas were histopathologically and immunocytochemically investigated with forty three 85 to 114 week-old F344 rats. Similar lesions were also studied by autoradiography with 10 Sprague-Dawley rats. Microscopically, the pancreatic lesion essentially was replacement of the exocrine tissue by proliferated duct-like structures. The often enlarged nuclei of epithelial cells lining these duct-like structures showed mitotic figures and active synthesis of DNA by autoradiography. Single acinus or small aggregates of endocrine cells were seen among these duct-like structures. There were also many transitional type cells between immature cubic cells resembling ductual epithelium and mature exocrine cells. These transitional type cells also revealed active DNA synthesis. The results indicate that the nodular lesions under study are involved with the regenerating change of the pancreatic tissue. Immature epithelial cells of duct-like structure appear to have the potential to differentiate into both ductual and endocrine cells. The possible morphogenesis of these regenerating nodules was discussed.