Malaria, a blood disease of humans, remains the world's most deadly infectious agent. The previous difficulties of working with human malaria in the laboratory were overcome in 1976 by the continuous in vitro cultivation of Plasmodium falciparum, the severest of all the malarias. Such in vitro cultures of P. falciparum will serve as the primary experimental material. Malarial parasites, living as they do within cells, must contact a suitable host cell, penetrate it, exploit its resources and then leave it. All of these events involve the structure and function of the membranes of the host cell and the parasite, yet this is the area about which the least is known. The proposed studies are designed to characterize the plasmodial components that initiate the process of red cell endocytosis. In addition, studies of the surface architecture of the malarial parasite and the red cell's outer membrane will be undertaken to provide a biochemical explanation for the known functional changes in the infected host cell. In vitro assays for merozoite factors that induce red cell endocytosis will be developed, and the characteristics of the endocytotic vacuole determined by immunocytochemical electron microscopy. Structural modifications in the red cell membrane will be evaluated by: a variety of electron microscopic markers, and chemical analyses for sialic acids, phospholipids, cholesterol; changes in the cytoskeleton will be studied by TEM, cross-linking and SDS/PAGE. The structural components, once identified, could be exploited for the development of chemotherapeutic agents that would specifically impair parasite function, e.g. block metabolite uptake, halt red cell endocytosis, and could contribute to an understanding of antigenic variation.