Complications arising from difficulty controlled bleeding and thrombus formation during procedures which require extracorporeal circulation with heparin as anticoagulant motivate the search for better hemostasis and anticoagulant technology. An enzyme (Defibrase), having a specific interaction with fibrinopeptide A such as to cause fibrin depletion in a soluble form, has been proposed as an alternative to heparin. Defibrase, in contrast to heparin, does not affect blood platelet function. Heparin and Defibrase as anticoagulants were compared in 8 h perfusion studies using arterio-venous extracorporeal blood circuits in dogs; the circuitry included pumps, membrane oxygenators and filters serially. Thrombus formation, in the filters and the oxygenators as well as pathology of the perfused animal were investigated. The results suggest that defibrase-like enzymes have potential for enhanced control of hemorrhagic and thrombotic phenomena. Although impeded by a latency of several hours before the full anticoagulant properties are developed in vivo, it appears that enzymatically mediated defibrinogenation of blood may be a valuable alternative to heparinization in extracorporeal circulation procedures.