The present report concerns current knowledge regarding immunopathogenesis that can be applied in the interpretation of histopathological changes in acute and chronic viral hepatitis. The histopathological features of viral hepatitis have not been changed and light microscopic examination remains essential for making a diagnosis and classification of chronic hepatitis and for the provision of objective parameters on grading and staging. However, new understanding and knowledge of viral pathogenesis, host immune responses, the biological behaviour of the causative viral agents and, in particular, viral interference in multiple hepatotropic viral infections must be taken into consideration in the interpretation of histopathological and immunopathological findings of liver tissues. This report also presents some histopathological analyses on multiple hepatotropic viral infections. It can be concluded that the diagnostic histological criteria for acute hepatitis remain applicable in such settings. However, the cause of acute flare up in chronic hepatitis could not be determined without clinical, virological and serological information. Routine histopathology cannot distinguish a new infection from an acute exacerbation due to a high level of viral replication or mutant virus. A repertoire of immunocyto-chemical stainings for viral antigens is helpful, but caution must be exercised in suggesting a specific viral aetiology due to the fact that suppression of pre-existing viral antigens can be pronounced when the new or concurrent infection is hepatitis C virus related.