Thirty-two transplant recipients with cytomegalovirus (CMV) infection documented by positive culture of blood and/or organs other than the liver were evaluated for hepatic involvement. Thirteen of the 32 (41%) had evidence of hepatic involvement with CMV. Inclusions alone were present in three patients; liver cultures alone were positive for CMV in three; and both were present in seven. Although the presence of CMV inclusions was the only histological feature that clearly separated the groups with and without hepatic involvement, two items helpful in finding inclusions were lobular aggregates of polymorphonuclear cells and portal karyorrhexic debris. The presence of liver involvement had a significant correlation with multiple organ infection, indicating it is a good marker of widely disseminated disease. This study indicates that liver histology and culture are useful and complementary methods for documentation of hepatic involvement (hence, tissue invasion) in immunocompromised patients with CMV infection.