So far the Cl inactivator, alpha 2-macroglobulin, antithrombin III (in the presence of heparin), and alpha 1-antitrypsin have been identified as inhibitors of plasma kallikrein; alpha 1-antitrypsin reacts slowly also with tissue kallikreins. Of the various naturally occurring kallikrein inhibitors the basic trypsin-kallikrein inhibitor of bovine organs, aprotinin (the active substance of Trasylol), has attained by far the most interest. This inhibitor, which is produced by mast cells, has unusual properties due to its compact tertiary structure. Additional topics of aprotinin and structurally related inhibitors discussed are the mechanism of enzyme-inhibitor complex formation, the production of chemical mutants of aprotinin, the structural basis of kallikrein inhibition, and selected aspects regarding aprotinin medication.