Experience with using intraarterial fibrinolysis in the treatment of occlusive disease of the popliteal artery and runoff vessels is limited. We describe the techniques and results in 25 patients with 30 fibrinolytic infusions of the popliteal and tibial arteries and compare them with the initial and long-term results of treatment using streptokinase and urokinase. The roles of catheter delivery systems and systemic heparin in the prevention of pericatheter thrombus were also studied. Urokinase was initially successful in 18 (90%) of 20 intraarterial infusions, whereas streptokinase was effective in 8 (80%) of 10 intraarterial infusions. Urokinase had the advantages of a shorter effective infusion time and fewer complications. Long-term follow-up was available in 20 of the successfully treated patients. Sixteen of these patients were doing well with an average follow-up of 27 months. The duration of the initial occlusion may be useful in identifying patients at risk for early reocclusion. No limbs were lost because of complications of therapy. The coaxial catheter system with a divided fibrinolytic dose provided protection against pericatheter thrombus, while systemic heparin was ineffective. Our results suggest that urokinase is more effective than streptokinase for intraarterial infusion in the treatment of occlusion of the popliteal and tibial arteries; this procedure is an important alternative to surgery or an adjuvant to surgery in selected patients.