Abstract: HCV has characteristics of rapid variablity.The amino terminus of E2/NS1 ofHCV(amino acids sequence 384～414),which is hypervariable with respect to both nucleotide andamino acid sequence,has been termed the E2 HV domain or HVR1. The E2 HV domain appears to bearapidly evolving region of the HCV genolnes which may contain linear neutralizing epitopes and theE2 HV are under immune selection, For further studies of the immunogenicity on E2 HV of HCV,weselected three peptide fragments from the full length of E2 HV region sequence and synthesized themwith SPPS method. The amino acid sequences are shown as following:P2:VDGDTHVT-GGAQAKTTNR(381～398);P9:STHVTGAVQGHSIRGTTSLFTSGPAQKIQ(384～412);P10:RTYTSGGTAGHTTSGITSLFSPGASQKIQ(384～412), From the results of ELISA and anti-peptideAbs of rabbit sera,we conclude that there are anti-E2 HV Abs in immune host but they could notneutralize HCV,so these Abs were not reactive with all E2 HV epitopes that resulted in immuneselection of escape mutants;the anti-E2 HV Abs,probably from the same genotype,contained somecommon structure in which E2 HV epitopes react with other anti-E2 HV Abs at 30%;the C-terminusof E2 HV region(398~412)caused the immune response to rabbits.