Although thrombolysis has been established for recanalization of acute and in part chronic peripheral artery occlusions, only smaller studies exist regarding the use of longterm rt-pa infiltration-thrombolysis. The objective of this study was to evaluate the benefit of additional long-term thrombolysis in patients with peripheral arterial occlusions for whom acute thrombolysis failed. From 1992 to 1997, 323 patients with peripheral arterial occlusions were treated with rt-pa (recombinant tissue-type plasminogen activator). When the thrombolysis failed during the first 3 hours, the thrombolytic therapy was continued as a long-term treatment with 3 mg rt-pa alternated by PGE, (2.1 mL/hr for 3 hours, concentration: 20 mu g/50 mL NaCl) every 3 hours. Additional heparin was applied in doses of 15,000 IE/24 hr or more to slightly increase the partial thromboplastin time. Angiographic controls were performed every 24 hours. If necessary, a final angioplasty was performed. In 142 of the 323 patients the occlusions were recanalized during the first 3 hours; 119 patients were treated with a long-term thrombolysis and in 72 (61%) a recanalization was ultimately achieved. Thus, the recanalization rate increased to 214 of 323 patients (p < 0.02). Mean treatment time was 2.8 +/- 2.2 days, range: 1 to 13 days. The rates of recanalization were not different in iliac, femoral, or crural arteries. Fibrinogen levels did not decrease during thrombolysis. Severe bleeding (with a decrease of more than 3 g/dL hemoglobin requiring transfusion) occurred in four patients after finishing the thrombolysis with short-term and in six with long-term therapy; two required surgical treatment. The 1-, 2-, and 3-year cumulative patency rates were respectively 90.1%, 74.2% and 64.9%. Patency rates in patients with acute or long-term thrombolysis were not different. A composite thrombolytic treatment using low-dose rt-pa in combination with PGE(1) offers significantly better results than an acute thrombolytic treatment alone. It can be an effective and practicable regimen in about 60% of patients in whom acute thrombolysis fails.