Percutaneous needle biopsy specimens of the liver from three elderly persons (aged 77, 71, and 66) demonstrated eosinophilic intracytoplasmic globules within hepatocytes, particularly in the periportal and periseptal areas. These globules were periodic acid-Schiff positive and diastase resistant, and were identified as alpha-1-antitrypsin by immunofluorescence technics. Two of the patients had cirrhosis, and identification of protease inhibitor (Pi) type by acid starch electrophoresis and crossed immunoelectrophoresis demonstrated SZ and MZ genotypes. The patient with SZ genotype also had a long history of chronic obstructive pulmonary disease. Pi-typing was not performed for the third patient, who did not have cirrhosis. The morphologic identification of alpha-1-antitrypsin disease in liver biopsies of persons of any age is important because of (1) possible multisystem involvement (hepatic and pulmonary), (2) increased frequency of hepatocellular carcinoma, and (3) implications for genetic counseling for other family members.