Work on vaccines against the pre-erythrocytic stages of the Plasmodium life cycle is based on the observation that immunization with irradiated sporozoites (IRR SPZ) is protective. Antibodies against several SPZ surface proteins can prevent SPZ from effectively invading hepatocytes; antibodies and cytolytic-T lymphocytes directed against at least 3 parasite proteins expressed in infected hepatocytes can kill infected hepatocytes; and cytokines can activate infected hepatocytes to kill the intracellular parasite. Work is in progress to identify additional pre-erythrocytic parasite targets and to develop methods for optimally inducing protective immunity against SPZ and infected hepatocytes. The goal is to construct a vaccine that protects by inducing antibody and cellular immune responses against multiple parasite proteins.