Monoclonal antibodies specific for luminal plasma membranes of acinar and duct cells of the exocrine pancreas were used to investigate changes in antigen expression during regeneration of the pancreas after acute pancreatitis and during fetal pancreatic development in mice. During regeneration after acute pancreatitis induced by supramaximal injections of cerulein or by a choline-deficient, ethionine-supplemented diet, morphologically identifiable acinar cells expressed the ductal antigen on their luminal surface, but at a lower level than this antigen is expressed on duct cells. As the pancreas regenerated, the ductal antigen was lost from acinar cells and was found only on duct cells. Characteristic tubular complexes formed in both pancreatitis models and were positive for the acinar antigen, demonstrating their acinar origin. In fetal pancreas, acinar cells between prenatal days 3 through 1, when zymogen granules were already abundant, expressed the duct-cell antigen on their luminal surface. By birth duct antigen was mostly present on ducts with only occasional label on acinar cells. The presence of a ductal antigen on acinar cells is associated with acinar-cell growth during regeneration and during fetal development and may reflect a less differentiated state.