Human alpha 2-macroglobulin-human pancreatic elastase II binding were investigated using a homologous substrate, human aortic elastin, in order to test the enzymatic activity. We demonstrated that two moles of alpha 2-M are required to inhibit one mole of HPEII when the enzyme is added to a mixture of elastin and alpha 2-M. In addition, when the elastase-alpha 2-M complex is prepared under some circumstances, it exhibits an elastinolytic activity.