Recanalization of the vascular lumen by means of local fibrinolysis is of major importance in the treatment of peripheral arterial occlusive disease. While urokinase and streptokinase have been extensively used for local fibrinolysis, there have been few studies of infiltration thrombolysis with genetically engineered tissue plasminogen activator (rt-PA). The aim of the investigation reported here was to establish whether there is any difference between urokinase and rt-PA in the short- and long-term outcome of local fibrinolytic therapy. One-hundred twenty patients (70 men, 50 women) with acute or subacute femoral (n = 21), femoropopliteal (n = 33), popliteal (n = 13) or popliteocrural (n = 53) thrombotic occlusions were randomized to local lysis using urokinase or rt-PA, and 6 months later follow-up investigations took place. Recanalization of thrombotically occluded vessels, particularly in the lower leg, was found more frequently, and after treatment of shorter duration, with rt-PA. Large local haematomas occurred in 8% of cases in the urokinase group and 15% in the rt-PA group. No serious haemorrhages were encountered in either group. Six months after treatment, the rt-PA group showed lower rates of Fontaine stage III and IV disease and amputation than the urokinase group, with a higher number of patients in Fontaine stage IIb. This study shows that local lysis with rt-PA yields better results than urokinase, not only in the short term but also 6 months later.