The bactericidal activity of normal serum was described in the 1880s by von Fodor, 1 Nutall, 2 and Buchner. 3 Nutall showed that the bactericidal activity of sheep blood against Bacillus anthracis was lost when blood was heated to 55°C. Buchner coined the term alexin to describe the heat-labile factor responsible for bacterial killing. In 1894, Pfeiffer and Issaef 4 demonstrated that whole blood from guinea pigs that survived challenge with Vibrio cholerae could protect naive animals from developing disease. The following year, Jules Bordet showed that the bactericidal activity of heated immune serum could be restored by fresh serum that itself had no intrinsic bactericidal activity. 5 Thus, the bactericidal activity of immune serum was dependent on a heat-stable factor as well as a heat-labile factor (alexin). The combination of heat stable antibody (Ab) and alexin was shown to cause hemolysis. 6,7 Bordet and Gengou described complement fixation and showed the loss of complement activity from serum in the presence of antigen-Ab complexes. 8 The term "complement" was coined by Ehrlich. Bordet was awarded the Nobel Prize for Physiology or Medicine in 1919 for his "discoveries relating to immunity," including the discovery of complement activity and complement fixation tests.Work on the complement system till the 1950s focused largely on the classical pathway. Although not appreciated at the time, the existence of the alternative pathway (AP) was suggested by experiments where cobra venom factor and zymosan consumed complement activity without affecting the heat-labile complement components. 9,10 Pillemer and his coworkers first characterized the