We report a trial in squirrel monkeys of 2 recombinant Plasmodium vivax malaria vaccine candidates based on the circumsporozoite (CS) protein. One recombinant (NSl81V20), produced in Escherichia coli, contains the repeat region of the CS protein. The other (VIVAX-1) recombinant is yeast-derived and contains the entire repeat domain and part of the surrounding N-terminal and C-terminal regions. Both antigens were administered with alum and muramyl tripeptide as adjuvants. No formulations caused toxic side effects. Both antigens, when administered with alum, induced high levels of sporozoite antibodies in all animals. Another group of animals was immunized with irradiated sporozoites alone. Upon challenge, a few immunized animals did not develop detectable parasitemia and others developed parasitemia only after a prolonged prepatent period. Monkeys immunized with irradiated sporozoites had higher levels of antibody but no increased protection. There was no correlation between protection and either antibody level or the in vitro proliferation of lymphocytes in response to the antigens. This is the first time P. vivax sporozoite vaccines have been tested in monkeys with a subsequent sporozoite challenge.