Abstract:To investigate a cellular mode of HCV‐infection in the liver and its pathological implications in relation to histopathological changes or clinical data, we studied the distribution of HCV‐RNA in the livers of 21 patients with HCV‐related chronic liver disease (chronic active hepatitis, 14 cases; cirrhosis, 7 cases) using thein situhybridization technique.In situhybridization was performed on 4% paraformaldehyde‐fixed frozen sections with digoxigenin‐labeled DNA probe deduced from the core region of HC–J4.In situhybridization showed positive signals in the liver specimens of 20/21 cases. The signals were localized in the cytoplasm of hepatocytes. The distribution pattern of positive cells was individually different, whereas the pattern was identical in the right and left lobes. There were no correlations of the HCV‐positive cell number with serum aminotransferase levels at biopsy or with genotypes of HCV. The positive hepatocytes were occasionally associated with infiltrating mononuclear cells, and they were sparsely distributed in the area of piecemeal necrosis. These findings suggest that factors such as host immunoreaction to the virus may be more important than its direct cytopathy in the pathogenesis of chronic hepatitis C vi