Different forms of hepatocellular proliferation are seen in fetal livers, massive hepatic necrosis, and nodular transformation (nodular regenerative hyperplasia) of the liver. In an attempt to characterize the proliferating cells in these conditions, we studied the expression of several antigens by immunohistochemical methods. Alpha-fetoprotein (AFP), alpha 1-antitrypsin (AAT), a hepatocellular export protein, carcinoembryonic antigen (CEA), a marker of bile duct epithelial cells, and hepatitis B virus antigens (HBsAg, HBcAg), were localized by the peroxidase-antiperoxidase method in 11 fetal livers, 10 cases of nodular transformation, and 7 cases of massive hepatic necrosis. AFP was the most prevalent antigen in fetal hepatocytes. Many hyperplastic hepatocytes in nodular transformation contained AAT, but not oncofetal antigens, supporting the differentiated hepatocellular nature of these cells. A similar staining pattern was seen in two-cell-thick plates of hepatocytes in massive hepatic necrosis. In contrast, the ductlike structures at the periphery of necrotic lobules contained both AAT and CEA, suggesting that these cells exhibit features of hepatocytes and bile duct epithelial cells. Therefore, the appropriate term for these regenerating cells appears to be "ductular" or "biliary hepatocytes".