Six liver biopsies from previously healthy adult patients with cytomegalovirus (CMV) mononucleosis were studied by routine light microscopy and by the immunoperoxidase technique for CMV antigen. Light microscopical findings consisting of a mononuclear portal and sinusoidal infiltrate, increased hepatocellular mitotic activity and minimal hepatocellular necrosis were consistently found. Less common features were granuloma formation and bile duct epithelial damage. Typical CMV nuclear inclusions and CMV antigen were identified in only one case, a patient with marked leukopenia secondary to CMV who had received corticosteroid therapy. The other five cases contained no inclusions and CMV antigen could not be identified by immunoperoxidase staining. This data suggests that, as with hepatitis B, viral antigen is not identifiable in acute CMV hepatitis in the immunocompetent host, perhaps due to active destruction of infected cells. The immunoperoxidase technique for CMV appears to be of little value in the diagnosis of acute CMV hepatitis.