The standard treatment for deep vein thrombosis (DVT) is anticoagulation. Although this usually stops thrombus progression, the clot must resolve by natural processes, which take weeks to months and often leave permanent venous damage. In an effort to remove thrombus more quickly and preserve venous function we have conducted trials of a thrombolytic agent, recombinant tissue plasminogen activator (rtPA, Alteplase), which is injected directly into the thrombi. This treatment has been effective and associated with only minor adverse events. However, because of the risk of bleeding rtPA has been given only to patients considered to have a very low risk for hemorrhage. To reduce the risk of bleeding we are now using a much lower dose of rtPA, which may also be just as effective or even more so than the previous dose because it may avoid plasminogen depletion. So far on this protocol we have treated only one patient. She received only 22 mg of rtPA distributed over 3 treatment sessions (compared with up to 150 mg given in earlier protocols). Her thrombi lysed extensively, and she has continued to be asymptomatic on oral anticoagulation. The protocol is approved for 21 patients.