Using the electron microscope and techniques such as negative staining and ferritin-labeling of specific antibody to individual complements, the spatial relationship of the terminal components to each other and to the lesions produced in red cell membranes by the action of complement will be investigated. Utilizing similar techniques, platelet membranes will be examined ultrastructurally in order to determine whether complement dependent lesions are produced during the process of clotting. If such lesions are visualized, experiments will be performed to delineate the significance of these membrane changes for platelet aggregation and fusion. Studies will be initiated to ascertain the role of complement in tumor immunology. In addition, ultrastructural analysis will be performed of tumor cell membranes subsequent to their interaction with antibody and complement. A cytotoxic assay will be developed utilizing tumor specific antibody and complement and in vitro experiments will be made to ascertain the possible advantage in such a system of chemical enhancement of the biologic activity of the complement system. Should enhanced tumor cell destruction result from such a modification, the possibility of in vivo application of this manipulation will be explored. Utilizing clinical material which will become available during the course of the program, the biologic and clinical significance of deficiency states of complement will be studied.