Tissue plasminogen activator (t-PA) developed from recombinant DNA technology is a highly effective thrombolytic agent. Its main clinical application is in the treatment of acute myocardial infarction (MI), with most beneficial results occurring in patients treated early after the onset of symptoms. When t-PA was compared with other thrombolytic agents, such as strep-, tokinase (SK) and anisolyted plasminogen streptokinase (APSAC), the data obtained from the mega trials (GISSI 2 and ISIS 3) revealed no significant difference in mortality. However, in the recent GUSTO trial involving 41,000 patients, t-PA-treated patients had a significantly lower mortality rate compared to SK-treated patients. Aggressive adjunctive therapy, including intravenous heparin in combination with aspirin, may have accounted for this difference.