We have characterized the circumsporozoite (CS) gene sequences of Plasmodium malariae China-1 CDC, isolated recently from a person who was infected 50 years ago in China, and P. vivax Chesson, isolated 48 years ago from a patient who had returned from New Guinea. These protein sequences were compared with the CS protein sequences of recently isolated P. vivax and P. malariae parasites. In a similar manner, we compared the previously characterized CS protein gene of P. falciparum clone 7G8, derived from a Brazilian isolate collected in 1980, with the CS protein genes of recent P. falciparum field isolates. In the case of the P. malariae CS protein gene, with the exception of an additional copy of major (NAAG) and minor (NDAG) repeat sequences and the presence of one copy of NDEG sequence, the China-1 CDC P. malariae parasite is similar to the Uganda-1 CDC isolate of 1982. In the nonrepeat region, changes were noted in two amino acid residues, one of which is also seen in a closely related monkey malaria parasite, P. brasilianum. In the case of P. vivax CS proteins, the nonrepeat region of the protein in Chesson strain shares identity with nearly 71% of the CS clones characterized from field isolates. In the P. falciparum CS proteins, the 7G8 CS protein sequence is identical to 75% of the genes of recent field isolates in the Th1R-N1 region. In the Th2R and Th3R regions, 34% and 55% of the CS clones analyzed, respectively, had changes at two amino acid residues. These results reveal that polymorphism in the CS protein of human malaria parasites may not undermine its use as a vaccine antigen, thus alleviating concerns of antigenic polymorphism in vaccine development.