Thrombolytic therapy has been shown to enhance survival in patients with acute myocardial infarction or cerebrovascular accident. Current agents, however, have several limitations including incomplete recanalisation, a high rate of reocclusion and significant adverse effects. In order to speed clot resolution, increase fibrin specificity and prolong half-life, new thrombolytics have been designed that are mutants of tissue-type plasminogen activator (t-PA). Additionally, staphylokinase and Desmodus rotundus salivary plasminogen activator ('bat-PA') have been isolated and tested. Another promising approach is to combine plasminogen activators with fibrin-specific antibodies in an attempt to concentrate thrombolytic activity at the site of thrombus. The combination of antifibrin antibody 59D8 and single-chain urokinase-type plasminogen activator has shown promise in a baboon model of arterial thrombosis. Studies are currently in progress or being planned to evaluate these approaches in humans with acute myocardial infarction to determine if the promising experimental results will lead to therapeutic advances.