Two promising novel recombinant tissue-type plasminogen activator (rt-PA) regimens for pulmonary embolism (PE) are being actively investigated: 100 mg/2 h as a continuous peripheral intravenous infusion, and bolus rt-PA, adjusted to weight, as a 2-min infusion. For deep venous thrombosis (DVT), less progress has been made in finding an optimal dosing regimen of rt-PA. Our mandate for the 1990s is to use the best possible thrombolytic dosing regimens in large clinical trials of PE and DVT. The primary objective of these planned clinical studies is to determine which patients with PE and DVT will benefit the most from thrombolysis followed by anticoagulation rather than anticoagulation alone.