The development of a hemolytic assay for the measurement of the inhibitor of the activated first component of complement (C1̄INH) and the isolation of a functionally pure preparation of plasma kallikrein have permitted the following observations: The C1̄INH inhibits the enzymatic activity of purified human plasma kallikrein on TAMe and on its natural substrate kininogen. The interaction of C1̄INH and kallikrein proceeds in a fashion similar to the interaction of this inhibitor and the first component of complement. The reaction follows a second order kinetics, resulting in the formation of an inactive stoichiometric complex of C1̄INH and kallikrein.

The finding that C1̄INH acts effectively against both the activated first component of complement and plasma kallikre in is consistent with the view that the absence of this control step may be responsible for the episodic activation of C1 as well as the elaboration of the pathogenic peptide in patients with hereditary angioedema (HAE).