The rate of complication and the time necessary to achieve thrombolysis remain major disadvantages of regional thrombolytic therapy. By lacing the entire length of arterial or arterial bypass graft occlusions in the lower extremities of 49 patients with one of two different bolus doses of urokinase (mean, 52,000 International U in 35 infusions = low-dose group [28 patients]; mean, 230,000 U in 23 infusions = high-dose group [21 patients]) prior to identical continuous infusions, it was possible to demonstrate a decrease in the time needed to complete thrombolysis from 33.6 hours in the low-dose group to 10.4 hours in the high-dose group (P less than .001). The total urokinase dose necessary for successful thrombolysis was also significantly less in the high-dose group (P less than .001). The major complication rate was 22.9% in the low-dose group and 8.7% in the high-dose group, although the difference was not statistically significant. The use of urokinase and a high-dose transthrombus bolus injection technique significantly accelerates thrombolysis, decreases the total urokinase dose needed, and may lower the major complication rate.