We report the first synthetic peptide vaccine eliciting strong CD8+ and CD4+ T lymphocyte responses in humans. The vaccine, representing the C-terminal region of the circumsporozoite protein of Plasmodium falciparum (amino acids 282–383) was well tolerated and strong sporozoite-specific antibodies were elicited. In addition, robust lymphocyte proliferation responses were equally elicited with concomitant in vitro production of IFN-γ, crucial in the elimination of the parasite. Most importantly, we also observed the development of CD8+ T lymphocyte responses decisive in the immunity to malaria. The latter finding opens new, possibly safer, avenues for vaccination strategies when a CD8+ T cell response is needed.