Serum hepatocyte growth factor (HGF) levels are increased in patients with liver diseases. HGF has been recently reported to stimulate production of acute phase proteins such as alpha 2-macroglobulin and albumin of hepatocytes in primary culture. To clarify whether serum HGF concentrations have any relation to concentrations of acute phase proteins, we measured serum HGF and acute phase proteins in chronic liver diseases where the synthesis of many plasma proteins is decreased with the decline of liver function. Eighty three patients with chronic liver diseases and 20 normal individuals were examined for serum HGF, albumin, C-reactive protein (CRP), alpha-fetoprotein (AFP), alpha 1-acid glycoprotein (alpha 1-AG) and alpha 2-macroglobulin (alpha 2-MG). Mean values for serum HGF in chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) were 0.37, 0.79 and 0.66 ng/mL, which were significantly higher than those in controls (p< 0.05, p< 0.0001 and p< 0.0001, respectively). The levels of CRP increased in parallel with the progression of chronic liver diseases. Levels of alpha 2-MG were not changed in patients with CH Or LC, while those in patients with HCC were significantly higher than in controls or LC (p< 0.01 and p< 0.05, respectively). Serum HGF showed a positive correlation with CRP and a negative correlation with albumin. However, no relations between HGF and alpha 2-MG were observed. These data suggest that serum levels of acute phase proteins such as albumin and alpha 2-MG are more closely associated with the degree of hepatic dysfunction than serum HGF levels.