Abstract Three recombinant proteins spanning the Plasmodium falciparum liver‐stage Ag‐3 (LSA‐3) were used to immunize Aotus monkeys. The proteins were delivered subcutaneously withoutadjuvant, adsorbed onto polystyrene 0.5 μm particles at a concentration of 2 μg per immunization. Control animals received glutathione‐S‐transferase formulated similarly. Animals were challenged as late as 5 months after the last immunization, by intravenous inoculation of 100,000 P. falciparum sporozoites of a strain heterologous to the one from which the immunogens were derived. Sterile protection was achieved in three of the five immunized monkeys but in none of four controls. Antibodies were at low titer, but reacted with the native parasite protein and were boostedby parasite challenge. Ag‐specific IFN‐γ secretion was detectable in all LSA‐3‐immunized animals in response to the LSA‐3‐derived Ag. The protection was apparently associated with high levels of IFN‐γ production in response to in vitro recall Ag. These results lend support to the vaccine potential of LSA‐3 indicated by previous results obtained in chimpanzees, as well as the value of yet another Ag‐delivery system. They also support the value of the Aotus model for the pre‐clinical development of pre‐erythrocytic‐stage vaccines.