Livers from 128 captive woodchucks (Marmota monax) that were negative for serological markers of woodchuck hepatitis virus (WHV) were examined grossly and histologically. Livers from 19 additional seronegative woodchucks were examined only grossly. The most common finding (61% of histological specimens) was mononuclear cells in portal areas. Moderate to severe portal infiltrates in association with similar scattered mononuclear cell aggregates and extramedullar hematopoiesis, were present in woodchucks that had extrahepatic inflammatory lesions. We concluded that these changes represent a response to a variety of chronic infections and are not specific for WHV infection. Other findings included parasitic granulomas, focal and diffuse lipidosis, bile duct proliferation, lesions secondary to cardiovascular compromise, and vasculitis. Two woodchucks had neoplastic lesions.