The serum complement system represents a major element of host defense mechanisms against invading pathogens. As such, it functions in concert with other elements of host defense mechanisms both of an immune or a nonimmune nature to preserve and/or restore normal function and health. The initial observations leading to the discovery of complement were made in the late 1800~’-~ when it was found that killing of bacteria by specific antibodies required an additional, nonspecific, thermolabile factor present in all normal sera. This discovery led to the concept that this nonspecific factor assisted the antibodies to carry out their bacteriolytic function. Hence, the term complement which literally means “that which completes or brings to perfection.” As a result of active research in the area during the last 25 years, the original concept of immune bacteriolysis has been completely revised. It is now well established that complement proteins are actually responsible for the formation of lethal cell lesions, whereas the role of antibody is to identify the invading cells and to initiate complement activation. Further, it is also well established that complement can kill bacteria and other pathogens such as protozoa, fungi, and viruses as well as cells of higher organisms even in the absence of antibody. More importantly, it is now well accepted that the contributions of complement to host defense are much broader than killing of cells. The system mediates a number of other functions essential to host defense such as release of histamine from mast cells, chemotactic attraction of phagocytic cells, and opsonization of cells and particles. Complement is a highly organized and tightly regulated system which like other mediator systems in the blood, such as the coagulation system, the fibrinolytic system, and the kinin-generating system, is activated in. a sequential,“cascade-like’’fashion. Fourteen distinct proteins participate in the activation sequence and at least six other proteins are responsible for the regulation and control of the system (recently reviewed in 4-7). This apparent complexity is contrasted by the functibnal simplicity of the complement system, which becomes evident when its participation in host defense is considered. With few possible exceptions, all the complement-derived biological activities that are relevant to host-defense are derived from two proteins, C3 and C5. These two complement components are structurally very similar. They both have a molecular weight of approximately 185,000.8~’0 Each has two disulfide-linked polypeptide chains termed (Y (110,000) and/3 (75,000). Their biosynthetic precursors are singlepolypeptide chain molecules. yl* lz Finally, available limited amino acid sequence data indicate extensive sequence homologies between C3 and C5. 13 The structural similarities between the two proteins make it likely that they represent gene