Defibrotide is a profibrinolytic agent which has potent stimulatory effects on vascular prostacyclin (PGI2) production and secretion. We have studied the effects of this substance on the morphological organization of venous thrombi by combining ultrastructural evaluation with histometric analysis. Thrombosis was induced by inserting a collagen-coated thread into the femoral vein of rabbits 2 h before sacrifice. The results show that Defibrotide is highly effective in reducing the size of the thrombus. This is due to combined profibrinolytic action and interference with platelet and leukocyte adhesion as indicated by results showing that: (i) large deposits of fibrin-like material are smaller and less abundant; (ii) platelet aggregates are smaller, and (iii) the density of leukocytes in thrombus is strongly decreased. Polymorphism is prominent in platelets which are indistinguishable from control suggesting that the primary site of action of Defibrotide is on adhesion. The inhibitory effect on leukocyte participation to the thrombotic process is probably due to PGI2 release and may be of relevance on maturation and aging of the thrombus.