Antithrombin is the most important direct inhibitor of blood coagulation proteinase activities. The origins of our current understanding of the nature of its inhibitory activity can be traced to the work of Abildgaard and of Rosenberg et al (1, 2) who isolated the protein from plasma, showed it could in-hibit coagulation proteinases and demonstrated that this inhibitory action could be greatly accelerated by heparin. Amino acid sequence composition determinations then pointed to its membership of a superfamily of related inhibitors, the serpins (3), that regulate proteinase activities in a number of processes, such as coagulation, the complement pathway, matrix remodelling, cell differentiation and inflammation. The detailed mechanisms of the inhibitory action of the serpins have now been suggested by images of surface topography of the protein family derived from crystal structure determinations (a 6).