The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, contraindications, and dosage and administration of tissue plasminogen activator are reviewed. Tissue plasminogen activator (t-PA) is a serine protease that binds to fibrin-plasminogen complex, catalyzing the conversion of plasminogen to plasmin. Unlike streptokinase or urokinase, t-PA binds slowly, if at all, to free circulating plasminogen. This clot specificity suggests t-PA will not produce a systemic lytic effect; however, clot specificity appears to be dose-related, and concentrations similar to those achieved in recent clinical trials have been associated with hemostatic defects. Most clinical trials have used a recombinant DNA product (rt-PA). In the treatment of acute myocardial infarction, intravenous infusions of rt-PA appear to be more effective than intravenous streptokinase. Similar rates of hemorrhage, reperfusion arrhythmias, and reocculsion have been reported. Contraindications to rt-PA use are similar to those for other thrombolytic agents. Preliminary studies of rt-PA in various thromboembolic disorders are encouraging. Marketing approval of a t-PA product (rt-PA, Activase, Genentech, Inc.) is expected in the United States by mid-1987. Clinical trials suggest that rt-PA is more effective and as safe as intravenous streptokinase in lysing occlusive coronary-artery thrombi; however, safety and efficacy appear to be dose-related, and further study is needed to determine the optimal dose.