Two synthetic polypeptides containing multiple B- and T-cell epitopes derived from the conserved regions of two vaccine candidate antigens namely MSA-1 and RESA of human malarial parasite P. falciparum were studied for immunogenicity and protectivity. Both constructs elicited strong antibody and lymphocyte proliferation responses in BALB/c mice immunized with the carrier-free peptides. In an ELISA, these peptides also bound antibodies present in the sera from the P. vivax infected humans as well as from the P. yoelii infected mice. Significantly, our data showed that immunization of mice with these P. falciparum peptide could impart partial protection against P. yoelii challenge infection. Our finding that synthetic peptides representing portions of P. falciparum antigens were capable of stimulating protective immune responses against rodent malaria suggests that murine malaria model P. yoelii may provide a suitable system for primary screening of potentially protective synthetic immunogens.