Aprotinin is a polypeptide from bovine lung which has been known since 1930, and which has previously been administered to humans as a relatively non-specific protease inhibitor in a number of disease states. In 1987, a remarkable use for this drug was realized, when by chance, it was discovered that by infusing large doses of aprotinin during cardiac surgery, it was possible to greatly reduce the bleeding which had hitherto been regarded as normal in such operations. The aim of this article is to briefly review the biochemistry and pharmacology of aprotinin, and to describe the background to its use in preventing postoperative bleeding. The use of aprotinin in reducing bleeding after cardiac surgery is then described in detail, and outlined for other types of major surgery. The possible modes of action of aprotinin in reducing bleeding are discussed, with particular reference to the bleeding which follows cardiac surgery. The profound effect of aprotinin, given in a novel dosage to reverse the postoperative haemostatic defect suggests that this drug may abolish the need for blood transfusions in most patients after major surgery. In addition, it is dear that aprotinin will provide a potent tool to probe some of the remaining mysteries of the haemostatic process.