Tissue plasminogen activator (t-PA) is a new intravenously administered thrombolytic agent currently being tested for emergency treatment of acute myocardial infarction (AMI). This report summarizes our clinical experience using t-PA to treat AMI in the emergency department and describes current protocols for its use in treating AMI. Between September 1985 and August 1986, t-PA was administered to 105 patients with AMI according to clinical research protocols. All were treated within six hours of the onset of pain. Thrombolysis was achieved in 80 patients (76%). Percutaneous transluminal coronary angioplasty was performed acutely for residual stenosis in 58 (55%). Thirty-three patients (31%) exhibited cardiac arrhythmias during treatment, 18 (17%) requiring emergency intervention. Periaccess hematoma developed in 50 patients (48%); transfusion of one or more units of blood was required in 22 of 97 (23%), excluding those undergoing urgent coronary artery bypass grafting. Overall 30-day survival was 94%. Recombinant t-PA appears to be an effective thrombolytic agent that may soon be standard emergency therapy for patients with AMI. Administration begun in the ED can achieve a high rate of reperfusion, but requires careful monitoring and the support of a coordinated acute cardiac care program, including emergency cardiac catheterization and cardiac surgery, to achieve the best results.