A total of 20,981 patients in 14 countries with suspected myocardial infarction (AMI) admitted within six hours from onset of symptoms, were randomized to recombinant tissue plasminogen activator (tPA) (100 mg over 3 hours) or streptokinase (SK) (1.5 MU over one hour). Half of the patients were also randomly allocated to subcutaneous heparin (12,500 U twice daily). The hospital mortality was similar with SK and tPA (8.5% vs. 8.9%), and similar with and without heparin (85.5% vs. 8.9%). Likewise, no differences were found in the number of cardiac complications. More strokes occurred with tPA (1.3%) than with SK (0.9%), while more major bleeds were seen with SK (0.9%) than with tPA (0.6%). More major hemorrhages were also observed with heparin (1.0%) than without heparin (0.5%), whereas, heparin did not affect the incidence of stroke or reinfarction. Fewer allergic reactions were observed with tPA (0.2%) than with SK (1.7%). It is concluded that tPA and SK are equally effective and safe for use, and should be recommended for treatment in patients with an AMI of less than six hours duration.