Current support or replacement therapies for fulminant acute hepatic failure are frequently very disappointing. In this study, human hepatic stimulator substance--a liver-specific growth factor--was partially purified from human fetal liver cells and characterized by its biological effects. Almost 70-fold protein content was purified with an approximately 80-fold increase in specific growth stimulator activity. Human hepatic stimulator substance proved to be heat-stable, protease-sensitive, organ-specific and species-nonspecific. Human hepatic stimulator substance produced a two- to threefold increase of 3H-thymidine incorporation into hepatic DNA when injected intraperitoneally into growing weanling mice (nonhepatectomized) or regenerating rats (34% hepatectomy). The effects of hHSS in reversing the lethality of D-galactosamine (1.6 gm/kg body weight)-induced hepatic necrosis in rats were further evaluated. A survival rate of 4% (n = 24), 41% (n = 12, p less than 0.05), 33% (n = 12, p less than 0.05), 31% (n = 13, p less than 0.05) and 18% (n = 11, p greater than 0.05) was observed when the rats were injected with 4 ml of saline intraperitoneally, 4 ml of human intact fetal hepatocytes (2.4 x 10(8] intraperitoneally, 4 ml of human hepatic stimulator substance intraperitoneally, 2 ml of twofold concentrated human hepatic stimulator substance intravenously and 1 ml of fourfold human hepatic stimulator substance intramuscularly, respectively, 20 hr after poisoning.(ABSTRACT TRUNCATED AT 250 WORDS)