We reviewed 40 liver biopsy specimens from 36 patients with non-A, non-B (NANB) hepatitis by light microscopy to characterize the histopathologic features associated with this condition. NANB hepatitis had been acquired from intravenous drug use (6 patients), transfusion (11 patients), sporadic (13 patients), and other routes (6 patients). The major pathologic diagnoses included acute hepatitis, chronic persistent hepatitis, chronic lobular hepatitis, chronic active hepatitis with or without cirrhosis, and hepatocellular carcinoma. Histopathologic changes seen in varied combinations in these specimens included acidophilic degeneration of hepatocytes (100%), fat (85%), formation of portal tract lymphoid aggregates or follicles (52%), bile duct damage (30%), and multinu-cleate giant hepatocytes (25%). Prominence of sinusoidal cells was variable, but often striking. Hepatocyte atypia (liver cell dysplasia) was noted in 17 specimens. These histologic parameters appear to be diagnostically useful when applied in appropriate clinical settings and will require reevaluation when serologic tests for NANB hepatitis become available.