Angioneurotic edema results from acquired or genetic deficiency of C1 inhibitor (C1 INH), a member of the serpin family of protease inhibitors. C1 INH is the only plasma protease inhibitor of activated C1r and C1s, the serine protease subcomponents of the first complement component. It is also the major inhibitor of plasma kallikrein and of coagulation factor XIIa. C1 INH consists of a single polypeptide chain of 478 amino acid residues. It is the most heavily glycosylated plasma protein; a large portion of the carbohydrate is O-linked to serine and threonine residues. Hereditary angioneurotic edema (HANE) occurs in individuals heterozygous for deficiency of C1 INH. Most patients have absolute deficiency of C1 INH (type 1 HANE), while others (15% of kindred) synthesize a dysfunctional C1 INH protein. The molecular genetic defects in the C1 INH gene in both type 1 and type 2 HANE currently are being defined. Acquired angioneurotic edema (AANE) also is of two types. One of these occurs in individuals with B-cell lymphoproliferative disorders (type 1) and the other is characterized by the presence of autoantibodies directed toward the C1 INH molecule.