Experimental evidence of the existence of liver-specific growth factors has been collected for more than two decades. Blood-borne growth-promoting activity of hepatocytes may be separated into plasma and platelet-derived factors. Several groups have observed the stimulation of hepatocyte growth in vitro by some platelet-associated activity, which was recently isolated from rat platelets as a 27-kDa protein called platelet growth factor (PGF). There is evidence of at least two different growth factors for hepatocytes derived from platelet-poor rat plasma, 'hepatopoietin' A and B. The partial purification of several other factors has been reported. One of these factors was prepared from the plasma of patients with fulminant hepatic failure. In addition to these 'humoral' factors, cytosolic growth-promoting activity has been partially purified by several groups. While the humoral factors described so far are only active on normal hepatocytes, the cytosolic 'hepatic stimulator substance' (HSS) also promotes the proliferation of differentiated hepatoma cells. In addition, it appears to depend on the permissive action of epidermal growth factor (EGF). None of the liver-specific growth factors except PGF has been purified to homogeneity. Thus, their significance for the control of the proliferation of normal and transformed hepatocytes is still an unsettled issue.