Human plasma contains an array of proteinase inhibitors which are utilized in the regulation of a host of biological activities, including coagulation, fibrinolysis, connective tissue turnover, and complement activation. The concentration of several of these inhibitors increase at varying rates in the acute phase state while others remain constant or actually decrease. Increases are presumably an attempt to retain rigid control over certain critical reactions, while decreases are probably due to inhibitor turnover either through consumption during complex formation or inactivation by other endogenous proteinases. Virtually all of these latter reactions take place in a reactive site loop which is an exposed region present in at least eight related serine proteinase inhibitors (Serpins) in plasma. Complex formation and inhibitor inactivation presumably act as signals for inhibitor production and turnover in the acute phase state. However, exactly how this initial stimulus for increased protein synthesis is manifested at the protein level remains to be established.