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