This study examines the response of 3 different groups of patients to anticoagulants: 50 patients previously treated with streptokinase for acute myocardial infarction (AMI) (group 1), 24 patients with AMI who had received anticoagulants without prior thrombolysis (group 2) and 11 subjects who received anticoagulants for noncoronary indications (group 3). No significant differences were detected between groups 2 and 3; therefore, they were combined for analysis. After streptokinase, patients required 37,755 +/- 1,516 (mean +/- standard error of the mean) U of heparin per day to achieve the desired activated partial thromboplastin time (APTT). The dosage was 30,294 +/- 1,089 U/day in patients without antecedent thrombolysis (p less than 0.001). Group 1 patients required 5 +/- 0.4 days until adequate anticoagulation was achieved, compared with 3 +/- 0.2 days in the control group (p = 0.01). Despite higher heparin requirements, group 1 patients had a lower APTT value than the other subjects (87 +/- 5 vs 101 +/- 6 seconds, p = 0.08). Group 1 patients required 5 +/- 0.3 days to reach anticoagulation with warfarin versus 4 +/- 0.2 days in groups 2 + 3 (p = 0.05). Comparison of groups 1 and 2 yielded similar, although smaller, differences. Patients treated with streptokinase for AMI seem to be partially resistant to anticoagulation, which may increase the risk of reocclusion.