Malaria remains a leading cause of human morbidity and mortality due to the inability of insecticides and chemotherapy/chemoprophylaxis to eliminate the vectors or disease caused by this protozoan parasite. In an effort to develop new methods of control, vaccines targeted to the various stages of the complex life cycle of Plasmodium have been developed. This review describes recent advances in the elucidation of cell-mediated immune mechanisms directed against sporozoites and liver stages of malaria parasites, their role in protection, and their relation to vaccine development. Recent data on the molecular basis of sporozoite-liver cell interaction are presented, and these may provide new approaches for chemoprophylaxis and immunoprophylaxis. We describe the role of the circumsporozoite protein, the major sporozoite surface antigen, in sporozoite movement and as a target of humoral immunity. The recognition of the circumsporozoite protein by human T cells is reviewed with emphasis on cytotoxic T cells and immune resistance against the exo-erythrocytic stage of the parasite. Earlier concepts regarding the polymorphisms of the circumsporozoite protein, the immunological relevance of this polymorphism, and predictions regarding vaccine development are reevaluated on the basis of recent data from different malaria endemic areas. Non-CS sporozoite antigens and liver stage antigens are discussed as potential targets for immune intervention. Recent experimental approaches such as multiple antigen peptides, recombinant live vectors, and new more potent adjuvants are considered for the development of more effective malaria vaccine formulations.