Acute liver injury was induced experimentally in rats by a single injection of a large amount of D-galactosamine. Hepatocellular damage was apparent from decrease of total serum proteins, marked release of transaminases into the circulation, precipitous decrease of total microsomal proteins, and intracellular enzymes such as cytochrome P450 and 5'-nucleotidase. In parallel with such hepatocellular damage, serum asialoglycoproteins accumulated markedly, reaching a maximum level 4 days after the injection and then decreased to the control level. In contrast to this increase, hepatic binding protein, a receptor in the liver which specifically recognizes asialoglycoproteins, decreased very much. At the same time, survival time of [125I]asialoorosomucoid intravenously administered into rats was much prolonged in inverse proportion to the decrease of the binding protein. From these results it was concluded that the decrease of the hepatic binding protein induced by galactosamine treatment is probably responsible for the marked accumulation of serum asialoglycoproteins.