Serums of patients with hereditary angioneurotic edema lack inhibitory activity against the esterase derived from the first component of complement. In one group of patients this lack appears to result from failure to synthesize the esterase inhibitor of the first component of complement, whereas in another group of patients an abnormal, nonfunctional protein is synthesized.

Serum complement has traditionally been defined as a four component system, Cq, C'2, C~3, and C~4. Although several investigators had suggested the existence of additional components (for review of earlier literature, see reference 1), only recently has unequivocal evidence been available supporting the further complexity of complement. The third component, C'3, was shown first to consist of at least two activities (1--4) and then three (5, 6), designated C~3a, C'3b, and C'3c. A highly purified protein,/31o-globulin (7), would appear to be identical with C'3a (5).Miiller-Eberhard and Kunkel (8, 9) and Taranta, Weiss, and Franklin (10) have described a new serum protein, distinct from the classical components of complement and designated the llS component on the basis of its sedimentation constant. In earlier work on the sequence of action of the components of complement (11, 12), the first component, C'I, was the first factor recognized to interact with sensitized erythrocytes. However, evidence has been presented that the I1S component participates in immune hemolysis at a stage even earlier than Ctl (8, 9), an observation which would appear to require revision of previous concepts of sequence.It is the purpose of this paper to report the resolution of Cq into three activities by chromatography on diethylaminoethyl (DEAE) cellulose of a euglobulin fraction of normal human serum. It will be shown that all three factors are required for reconstitution of Cq activity in several hemolytic systems and for generation of Cq esterase in the absence of antigen-antibody complexes (13).

The fraction of human serum designated as C'1 esterase inhibitor is known to inhibit the action of C'1 esterase, a plasma kallikrein, and PF/Dil, an enzyme in plasma enhancing cutaneous vascular permeability. In the present study, C'1 esterase inhibitor has been found to block the actions of plasmin and the C'1r subcomponent of the first component of complement, and to retard the generation of PF/Dil. No inhibition of blood clotting or of the generation of plasmin was demonstrable.