The DNA fragments encoding the preS epitopes of HBV surface antigen were fused to the HBc gene and expressed in E. coli under the control of the tac promoter. The products were analyzed by ELISA and Western blotting, which confirmed that the hybrid proteins were expressed as expected. Analysis by electron microscopy and CsCl density gradient ultracentrifugation revealed that all fusion proteins were able to form particles, only with a slightly lower density than the native multimeric HBc. Partially purified fusion particles were then used as immunogen to Balb/c mice and high titer antibody against the preS1(21-47) epitope was observed, which demonstrated that the immunogenictiy of preS1 (21-47) could be greatly improved when fused in the el loop in HBc protein.