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. ? ? Since the last report we have enrolled 3 patients, for a total of 11. Our diagnostic evaluation of one of these, however, did not confirm the diagnosis of DVT. The other two patients were successfully treated. Therefore, so far, extensive thrombolysis had been achieved with low doses of alteplase in 9 of 9 patients treated. The protocol is approved for 21 patients.