Bcl-2 protein blocks apoptosis and is involved in human intrahepatic bile-duct development. Formalin-fixed, paraffin-embedded archival tissue from 42 HBV and HCV hepatitis [20 acute AH, 22 chronic hepatitis (CH)], 12 active cirrhosis (CR) and 20 hepatocellular carcinoma (HCC) was immunostained for bcl-2 protein. In all cases, bcl-2 protein was detected in portal and intralobular lymphocytes but not in hepatocytes or Kupffer cells. Bcl-2 was positive in the cytoplasm of small portal bile ducts of chronic hepatitis, while it was strongly expressed in newly formed bile-ductules of the limiting plate, mainly in CH with marked activity and CR. Bcl-2 was detected in small bile ducts in only one case of acute hepatitis and was not detected in any case of HCC. Bcl-2 seems to be involved in the regulation of growth and apoptosis of cholangiolar cells. Its expression in small bile ducts and in newly-formed ductules especially in CH with marked activity and CR, implies that the embryonic model of intrahepatic bile duct development may be recapitulated in chronic hepatic disease. Moreover, it supports evidence for the existence of the controversial long-lived stem population in the liver. Bcl-2 does not seem to be involved in hepatocarcinogenesis.