Hepatocyte Growth Factor (HGF), which is a most potent growth factor for primary cultured hepatocytes, may act as a trigger for liver regeneration. After 70% of the rat liver was removed, HGF activity in the remnant liver began to increase within 24 h. In parallel with the activity, the HGF mRNA level in the remnant liver increased at 12 h after the operation and reached a maximum at 24 h. Increases in HGF activity and in the mRNA level were much lower and later than those in the liver of rats with hepatitis induced with CCl4. However, the first increase in HGF activity in the plasma of hepatectomized rats was noted 3 h after the resection, that is much earlier than the initial DNA synthesis in the remnant liver. Thus, while HGF production was induced in the remnant liver during regeneration after partial hepatectomy, the initial trigger may not be the liver-derived HGF, rather, it may be HGF derived from extrahepatic organs, via blood circulation.