Sterile immunity against malaria has been obtained in mammalian hosts exclusively through vaccination with whole parasite preparations. Induction of complete protection against challenge was obtained using sporozoites attenuated by irradiation or genetic manipulations. It has been demonstrated recently that immunization with normal sporozoites under chloroquine cover confers sterile protection in mice and humans, using substantially fewer parasites and injections than with irradiated sporozoite immunization. Subsequently, it was shown that other drugs can substitute for chloroquine. We describe the immunization protocol using live sporozoites under chloroquine cover, which confers sterile immunity in rodents.