The life cycle of malaria parasites within their mammalian hosts is characterized by a high degree of developmental differentiation. An uninterrupted natural infection proceeds through three morphologically distinct stages: the sporozoite, the exoerythrocytic forms, and the blood stages. When malaria-infected female Anopheles mosquitoes bite the appropriate host, the infection is initiated by the entry of sporozoites into the circulation, where they are quickly disseminated around the body. In contrast to naturally acquired immunity, however, inoculation of some laboratory host models with malaria sporozoites attenuated by X-irradiation can confer protective immunity to viable sporozoite challenge. The proposition that solid immunity operates best when innate immunity is already high is obvious.