Infection with hepatitis B virus in man is a major health problem of worldwide concern. Its involvement in chronic liver disease and primary hepatocellular carcinoma among carriers signifies the importance of investigating the basic biology of this virus, which is crucial to the development of safe, economic and practical procedures for control of HBV infection. The general aim of the proposed studies is to continue to understand the genetic structure of HBV genome, investigate the mechanisms of viral pathogenesis and carefully examine the oncogenic role of HBV in hepatocarcinogenesis. The major emphasis will be placed on the development and extensive use of expression vectors programmed to synthesize HBV genes in mammalian cells. Approaches will be designed to determine DNA sequences with regulatory functions, enhancer functions and functions whose expression leads to the malignant transformation of cells in culture.