Both transforming growth factor α (TGFα) and hepatocyte growth factor (HGF) can induce hepatocyte proliferation experimentally in vitro and in vivo. In human, however, serum HGF levels are increased after hepatic necrosis and dysfunction or systemic inflammation, whereas serum TGFα levels are increased in association with the degree of liver regeneration (Hepatology, 15: 1, 1992; Gastroenterology, 103: 1621, 1992; Hepatology, 18: 304, 1993). It is suggested that TGFα and HGF contribute to liver regeneration through different mechanisms. To test this hypothesis, we measured hepatic contents and circulating levels of these growth factors in the following three rat models of liver growth: two-thirds partial hepatectomy (PH), a single administration of carbon tetrachloride (CCl 4 ) and ad libitum oral administration of phenobarbital (PB). Hepatic contents and serum levels of TGFα were increased in all three models along with the extent of hepatocyte mitosis. In case of HGF, hepatic contents and plasma levels increased earlier than in TGFα in rats after PH and CCl 4 treatment. However, in rats treated with PB, hepatic HGF content showed no increase despite of significant increase in plasma HGF levels. In conclusion, TGFα may regulate hepatocyte proliferation through different mechanisms from HGF.