The hepatic histopathology was studied in 125 patients with Hodgkin's disease to determine whether there are any features other than Reed-Sternberg (RS) cells that might aid in the diagnosis of hepatic involvement by the neoplastic process. Liver biopsy specimens from 41 patients with Hodgkin's disease in the liver were compared with biopsy specimens from 84 patients without hepatic involvement. Patients with hepatic involvement by Hodgkin's disease are much more likely to have histologic evidence of portal infiltrates larger than 1 mm in diameter (78% versus 1%), acute cholangitis (85% versus 4%), portal edema (90% versus 8%), and portal infiltrates with a predominance of atypical lymphocytes (78% versus 12%) than patients with Hodgkin's disease who do not have hepatic involvement. When these features are observed alone or in combination in a liver biopsy specimen from a patient with proven or suspected Hodgkin's disease, a diligent search for RS cells is indicated, with serial sections and repeat biopsy if necessary.