A family of cDNA sequences derived from hepatitis C virus (HCV)are provided. These sequences encode antigens which react immunologicallywith antibodies present in individuals with non-A non-B hepatitis (NANBH), butwhich generally are absent from control individuals or individuals infectedwithhepatitis A virus (HAV) or hepatitis B virus (HBV} The HCV cDNAsequences show homology with Flaviviruses, but lack substantialhomology with hepatitis delta virus and HBV. The HCV cDNA sequences areuseful for the design of polynucleotide probes, and for the synthesis ofpolypeptides to be used in immunoassays. These probes andpolypeptides may be useful for the diagnosis of HCV induced NANBH, and forscreening blood bank specimens and donors for HCV infection. In addition,thesecDNA sequences nay be useful for the synthesis of immunogenic polypeptideswhich may be used in vaccines for the treatment, prophylactic and/ortherapeutic,of HCV infection. Polypeptides encoded within the cDNA sequences may alsobe used to raise antibodies against HCV antigens and for the purification ofantibodies directed against HCV antigens. These antibodies may be useful inimmunoassays for detecting HCV antigens associated with NANBH inindividuals, and in blood. Moreover, these antibodies may be used fortreatmentof NANBH in individuals. The reagents provided in the invention also enabletheisolation of NANBH agent(s), and their propagation in tissue culture systems.Moreover1 they provide reagents which are useful for screening for antiviralagents for HCV, particularly in tissue culture or animal model systems.