Recurrent chest pain with new ST-segment elevation was observed in 26 of 652 patients (4%) with myocardial infarction in a clinical trial of alteplase (recombinant tissue-type plasminogen activator; 100 mg) and aspirin with or without heparin. Clinical and electrocardiographic signs of reocclusion were treated with a second dose of alteplase: 50 mg in 20 patients with signs of reocclusion < or = 24 hours after initial therapy, and 100 mg in 5 patients with signs between 24 and 77 hours, and in 1 patient with early signs of reocclusion. Pain and ST changes disappeared within 100 minutes (median 50). D-dimer determinations in 15 patients were increased, indicating activation of the coagulation system. Signs of reocclusion occurred despite adequate anticoagulation with heparin in 5 of 11 patients in whom coagulation measurements were available. No excess bleeding was observed in patients who received a second dose of alteplase. Retreatment with alteplase is feasible and provides an alternative for angioplasty in patients with clinical and electrocardiographic signs of reocclusion early after thrombolytic therapy.