In five patients with terminal liver failure, replacement of the diseased liver with a well functioning homograft restored markedly depressed total complement and C4 and C3 to normal levels. Concomitantly, C5 protein also increased. Postoperatively, two patients developed a marked drop in C4 and C3 probably in relation to homograft rejection. In contrast, serum hepatitis and biliary obstruction were not accompanied by significant changes. It is concluded that the liver is an important source of synthesis of C4, C3 and C5 and that complement assays might aid in otherwise equivocal diagnosis of hepatic homograft rejection.