W ITHOUT question, degenerative vascular disease remains the major cause of death and morbidity in the Western world. In the United Kingdom, cardiovascular disease is responsible for about 50% of all deaths in men aged 45-54 yr, and this must be compared with only 25% of deaths in this age group resulting from cancers.’ Although little direct proof exists, it is assumed that the primary function of the fibrinolytic system is, as the term implies, the removal of unwanted fibrin and the theoretically, therefore, the prevention, limitation of growth, and final dissolution of thrombi. The fibrinolytic system may be important even in the initial stages of thrombus development, since it has been demonstrated that fibrin formation is a necessary factor for the stabilization of platelet aggregates.* It is postulated that in vivo an equilibrium normally exists between coagulation and fibrinolysis3 and that an upset in this balance, by for example, a defect in the fibrinolytic system, could predispose to thrombus formation. Defective fibrinolytic activity has been demonstrated in a proportion of patients with degenerative vascular disorders both venous4” and arterial.6 Although the exact relationship between disordered fibrinolysis and vascular disease is far from clear, theoretical considerations of the nature of formation and evolution of thrombi have led to the suggestion that, by enhancing fibrinolytic activity, it may be possible to prevent thrombi forming and at least limit their extension. Intense plasma fibrinolytic activity can be induced readily with streptokinase or urokinase, but these agents must be injected and are useful only in major acute thrombotic situations. Neither of them have any place in the long-term prophylaxis of degenerative vascular lesions. Other means of increasing fibrinolytic activity have therefore been sought. A large number of compounds have been examined and found in vitro to have fibrinolytic activity.’ However, relatively few synthetic compounds have been tested in vivo, and while many of these do produce “fibrinolytic enhancement” with most synthetic compounds, this appears to be a transient phenomenon and of no long-term use. It is the purpose of this review therefore, not only to present information on those synthetic agents currently available, but to discuss possible future developments and to assess the likely benefit to be gained from long-term fibrinolytic prophylaxis.