Studies conducted between 1971 and 1975 showed that attenuated sporozoites can induce protection against human malaria. Three volunteers were protected against challenge with either a homologous or heterologous strain of Plasmodium falciparum after being exposed to a total of 440-987 X-irradiated mosquitos on 6-8 occasions over a period of 10-38 weeks. Protection lasted for at least 8 weeks, but not 16 weeks, after the last immunization with irradiated sporozoites. Another 7 volunteers were not protected against challenge with a homologous strain after exposure to a total of fewer than 200 irradiated mosquitos, infected with either P. falciparum or P. vivax, on 2-4 occasions over a period of 4-17 weeks. These studies provide an encouraging basis for pursuing the development of a sporozoite vaccine against human malaria.