Reported are the results of a trial in squirrel monkeys of 2 Plasmodium vivax malaria vaccine candidates based on the circumsporozoite (CS) protein, namely, rPvCs-2 and rPvCS-3. Compared with an earlier recombinant P. vivax CS construct, rPvCS-1, rPvCS-2 has an additional 24 amino acids at the C-terminal, which includes the thrombospondin region of homology and a putative T cell epitope. The rPvCS-3 was generated from a chemically synthesized gene that contained an additional 54 amino acids at the amino terminus and terminates at the same carboxy-terminal amino acid as rPvCS-2. In addition, rPvCS-3 contained only 1 each of the repeat sequences DRADGQPAG and DRAAGQPAG. Both antigens were administered with alum as adjuvant. Neither formulation caused toxic side effects and both recombinant molecules induced high antibody titers. Two monkeys were protected against sporozoite challenge by immunization with rPvCS-2 antigen, while none of the rPvCS-3 immunized animals displayed any degree of protection. While there was no correlation between protection and antibody titer or the in vitro proliferation of lymphocytes in response to the antigens, this is further evidence to support the role of the repeating epitopes in generating protective immunity.