Purified, irradiated, metabolically active sporozoites of Plasmodium falciparum (PfSPZ) have been administered to 80 volunteers through subcutaneous or intradermal routes. This PfSPZ vaccine has been shown to be safe but of low immunogenicity and hence protective efficacy as shown after challenge with infected mosquitoes. Intravenous delivery of PfSPZ in nonhuman primates induced memory CD8(+) and CD4(+) T cells specific for PfSPZ that reside in the liver. Further studies using PfSPZ and the intravenous route in humans are warranted to fully explore the potential of purified, attenuated sporozoites for malaria vaccine development.