Hepatocyte growth factor (HGF) was first described as a hepatotrophic factor in partially hepatectomized rat plasma in the early 1980's and was purified from plasma of a patient with fulminant hepatic failure and from rat platelets in 1986-1987. Recent progress has revealed that HGF is the same protein as scatter factor and tumor cytotoxic factor, and is now known to be a broad-spectrum growth factor which stimulates cell growth not only of hepatocytes but also of many other types of epithelial and endothelial cells. In this review, however, we concentrate on the role of HGF, mainly human HGF, on liver regeneration after injury. In humans, plasma levels of hHGF increase to greater than 10 ng/ml during severe liver disease such as fulminant hepatic failure and decrease rapidly to normal levels when the patients recover from the disease. In less severe liver damage such as occurs in acute hepatitis, levels of hHGF in plasma increase to 0.5-1 ng/ml which is approaching the half maximal concentration for the stimulation of DNA synthesis in human hepatocytes in culture. Thus, HGF is believed to be involved in control of liver regeneration. Although the cell type(s) which produces HGF during liver disease is not yet identified, it is possible that circulating leukocytes or splenocytes are responsible. Synthesis of HGF is though to be regulated by a putative inducer(s) derived from damaged liver tissue. A control mechanism for HGF production during liver disease is proposed.