Intra-arterial thrombolytic therapy is an important advance in the treatment of arterial occlusive disease. Reports of results, morbidity, and mortality have been highly variable. This review was undertaken to assess the recent results of thrombolytic therapy with urokinase (UK) at our institution. From 1988-1992, 42 lower extremities in 41 patients with severe peripheral vascular disease underwent intra-arterial thrombolytic therapy. Sites of occlusion consisted of 6 iliac, 21 superficial femoral, 11 popliteal, and 20 infra-popliteal segments. Lytic therapy consisted of a regional infusion of UK with concomitant heparin anticoagulation. The most common UK loading dose was 250,000 units (60,000-750,000) followed by a continuous infusion of approximately 100,000 units/hour (60,000-240,000) for up to 72 hours. Technical success, defined as partial or total resolution of the arterial occlusions, occurred in 26 (62%) limbs. A concomitant endovascular procedure was required in 19 extremities following successful lysis. Immediate clinical success, defined as restitution of a distal pulse or increase in ABI > 0.10, occurred in 22 of 26 technically successful procedures. The four clinical failures and all 16 technical failures required either a major amputation or revascularization. There were 18 major complications in 18 patients (43%): seven thromboembolic, two arterial dissections, nine hemorrhagic. Seven hemorrhagic complications required transfusion of 1-6 units of blood, and two deaths occurred due to postprocedural hemorrhage, shock, and myocardial infarction. Hemorrhage was not related either to the dose of UK or the duration of UK infusion. A combination of thrombolysis and endovascular intervention can be of significant benefit in selected patients with extremity ischemia. However, complications are frequent and may be lethal.(ABSTRACT TRUNCATED AT 250 WORDS)