In a randomized single-blind study, 13 healthy adult volunteers were subcutaneously immunized with 2 or 3 single 50 or 400 micrograms doses of a Plasmodium falciparum recombinant vaccine candidate designated 5.1-[NANP]19. The vaccine caused transitory reactions at the injection site. Eight (62%) volunteers had a greater than or equal to 4-fold increase of antibody titer against sporozoites in immunofluorescence assay, all 13 seroconverted in IgG enzyme-linked immunosorbent assay against [NANP]50 antigen, and in 6 (46%) a lymphocyte proliferation index greater than or equal to 3 against 5.1 antigen was observed. Seven volunteers were challenged with mosquitoes infected with P. falciparum. All developed detectable parasitemia after 7 to 12 days and all received drug therapy within 24 hours. One volunteer with a cellular response to 5.1 had two negative in vitro parasite cultures before treatment, despite overt parasitemia. He was the only challenged volunteer who remained free of malaria symptoms.