Structural and functional changes during liver regeneration have been studied extensively in experimental animals following partial hepatectomy or hepatic injury induced by noxious substances. These observations have been extended to evaluate abnormalities of liver regeneration which contribute to chronic hepatitis, cirrhosis and/or liver cancer in man. This is facilitated by the simultaneous perfusion of flash frozen percutaneous biopsies or explanted liver in an acrylic chamber with tritiated thymidine and proline to evaluate DNA and collagen synthesis, respectively. Such investigations indicate that chronic liver damage is associated with replication of mesenchymal, ductular and parenchymal cells, accompanied by increased fibrogenesis. The regenerative response of the liver after noxious injury in experimental animals and man is associated with the release of cytokines, increase of growth response genes and change in telomerase activity. The ability to monitor morphological, genetic and biochemical parameters provides new information on the kinetics of the reparative process in hepatobiliary disease. Abnormal liver regeneration and its untoward effects including tumorigenesis may be modified by altering nutrients, blocking antigens or receptors, and inhibiting metabolites which regulate cell replication and collagen deposition.