Data on biochemistry, physiological significance and clinical investigations of two main inhibitors of proteinases in human blood serum (alpha 1-antitrypsin and alpha 2-macroglobulin) are reviewed. Physico-chemical properties of the inhibitors, mechanisms of their interaction with proteinases and methods for determination are discussed. Modification of the specificity of some proteinases by alpha 2-macroglobulin, which probably plays a significant role in the regulation of enzymatic systems of proteolysis in blood, is considered. The use of the inhibitors of proteolysis for diagnostics of pathological processes is discussed. Data on the alpha 1-antitrypsin deficiency and its relation to the development of degenerative diseases in lungs are reviewed.