We examined the humoral immune response to recombinant structural proteins of hepatitis C virus (HCV) such as C, El and E2 in immunized mice. Mice showed high induction of antibodies against these three structural proteins. Conformational and/or linear epitopes of these regions showed high responses in mice. Comparison with patients revealed higher anti-El and anti-E2 responses in mice and 15 immunoreactive peptides which are unique to mice, especially 11 peptides from the E2 region. The hydrophilic regions of these proteins were found to be the most immunogenic.Therefore, the murine immune system against recombinant El and E2 glycoproteins was distinct from those of patients in natural infection, and may be a target to find protective activity against HCV infection.