The vaccine directed against human chorionic gonadotropin (hCG) has previously undergone clinical test demonstrating the feasibility of the approach in preventing pregnancy in women. Some individuals, however, did not response adequately despite employing highly immunogenic bacterial toxoids as carriers. In this study, we investigated the potential of three copies of C3d as a new molecular adjuvant to enhance the immunogenicity of hCG beta protein antigen. The antibody response to the hCG beta-C3d3 fusion protein immunization was compared with those resulting from immunization with the hCG beta alone and the hCG beta plus CFA/IFA either in BALB/c mice or in C(57)BL/6J mice. Our results showed that the fusion of C3d3 to hCG beta protein antigen resulted in a significant elevation of the serum anti-hCG beta antibody level in the two mouse strains and the antibodies were capable of effectively neutralizing the bioactivity of hCG. The immunization with C3d3 as a molecular adjuvant favored Th2 bias of immune response. The immunity-enhancing effect of the C3d3 was 10-fold (initial) and 20-32-fold (booster) greater than CFA/IFA. These findings indicated that fusion of C3d3 to hCG beta, as a means of harnessing the adjuvant potential of the innate immune system, may improve immunogenicity of the hCG beta contraceptive vaccine, which is useful to produce a cost-effective vaccine and for the less-responsive population.