The overall objectives of this research proposal are to study, by electron microscopy, 1) the localization of surface and intracellular protective antigens of the erythrocytic stages and gametocytes of Plasmodium by the use of monoclonals and cryo-ultramicrotomy, 2) the effects of histidine analogues on the structure of knobs appearing on the membrane of erythrocytes infected with P. falciparum, 3) the role of erythrocyte cytoskeleton during merozoite invasion by the use of Imposil-antibody conjugates and 4) the effects of colchicine and taxol on the formation of zygotes and ookinetes. The identification and localization of protective antigens within the parasites will facilitate further characterization of the antigen necessary for the development of malaria vaccine. The study on the effects of histidine analogues will advance our knowledge on the alteration of host cell membrane and may produce a clue enabling the prevention of such host cell membrane alterations. Understanding the role of the erythrocyte cytoskeleton during merozoite invasion may reveal a basic mechanism of host cell invasion. The investigation on the effects of colchicine and taxol on gametogenesis and zygote transformation will contribute a better understanding of these processes, particularly the role of microtubules. Thus, these investigations should provide answers to a number of basic questions on the hostmalarial parasite interaction and immunological mechanisms in malaria and may lead to the discovery of better methods for the control of malaria.