Post-transfusion hepatitis remains a major medical problem in spite of screening for hepatitis B surface antigen in the blood of prospective donors. Approximately ten percent of post-transfusion hepatitis is due to HBV, the remaineder is mainly due to non A non B hepatitis. Both heaptitis B and non A non B heaptitis can cause chronic heaptitis and epidemiological studies have suggested a casual relationship between HBV and heaptocellular carcinoma. Integration of HBV DNA in productively infected liver (acute and chronic) and hepatocellular carcinoma will be analyzed by 1) cloning HindIII digested DNA fragments which contain viral sequences but are larger than viral DNA, 2) determining whether the cloned fragments contain HBV DNA linked to cell DNA, 3) identifying the junction sites of intergration in viral and cellular DNA by sequencing, 4) assessing the orientation of the integrated viral DNA,. and 5) assessing the ability of cloned integrated DNA graments to transform cultured cells. Particles resembling picornaviruses have been found in the serum and liver of chimpanzees with on A non B hepatitis. A non A non B hepatitis virus will be investigated by: 1) growing the virus in tissue culture, 2) identifying and radioactively labeling the viral nucleic acid, and 3) clining the viral nucleic acid in E. coli. The cloning of viral nucleic acid will permit: a) the development of a DNA probe to assay for the virus in blood, tissue, and tissue culture and b) an attempt to express viral genes in E. coli. A probe may be used to investigate the molecular biology, epidemiology, host range and course of infection of the virus. Viral antigens synthesized in E. coli will be used for the development of a serological screening test for the virus.