As part of a study of community-acquired non-A, non-B hepatitis, liver biopsy specimens of 29 anti-HCV positive and four anti-HCV negative patients were evaluated in order to characterize the histopathologic changes of chronic hepatitis C. Liver biopsies were performed 6 to 46 mo after onset of the disease and repeat biopsies were obtained in 10 anti-HCV positive patients. The histologic diagnoses were chronic persistent hepatitis (45%), chronic active hepatitis (35%), and chronic lobular hepatitis (21%). Irrespective of the tissue diagnosis, the majority of the patients showed characteristic histologic abnormalities in the liver, particularly damage of the small and medium-sized bile ducts (76%), lymphoid aggregates in portal tracts (45%), enlarged macrophages (48%), and steatosis (31%). In 59% of the patients, two or more of these histologic abnormalities were combined. Similar histologic changes have previously been observed in non-A, non-B hepatitis, but only uncommonly in hepatitis A or hepatitis B. We conclude that the histopathologic findings in chronic hepatitis C are highly characteristic, although not pathognomonic.(ABSTRACT TRUNCATED AT 250 WORDS)