The C-terminal 42-kDa fragment of the merozoite surface protein-1 of Plasmodium falciparum (PfMSP-1(42)) was expressed as a recombinant protein in Escherichia coli and purified to near homogeneity. We tested the immunogenicity of recombinant PfMSP-1(42) in three clinically acceptable adjuvants (Montanide ISA 720, alum and MF59) in mice and in rabbits. High antibody responses were obtained with two adjuvant formulations with IgGl being the predominant immunoglobulin isotype. Significant T-cell proliferation responses were also observed. Competitive enzyme linked immunosorbant assay (ELISA) showed the presence of both invasion and processing inhibitory antibodies in sera obtained from the immunized rabbits. Passive immunizations of mice with anti-PfMSP-1(42) IgG purified from the rabbit-sera were found to be protective against a parasite challenge with P. berghei/P. falciparum chimeric line (Pb-PfM19) that expresses Plasmodium falciparum MSP-1(19). These findings may be useful for the development of a malaria vaccine based on Plasmodium falciparum MSP-1(42).