The relation between the level of residual plasma fibrinogen and coronary artery reperfusion after 750,000 IU of intravenous (i.v.) streptokinase (SK) was examined in 76 patients with acute myocardial infarction. Both the frequency and rapidity of reperfusion were greater in the 53 patients in whom the residual fibrinogen level was 50 mg/dl or less (low fibrinogen) than in the 23 patients in whom it was more than 50 mg/dl (high fibrinogen). Reperfusion occurred in all 53 patients in the low-fibrinogen group, compared with only 15 patients in the high-fibrinogen group (p < 0.001). The interval from initiation of SK to clinical signs of reperfusion was 50 ± 34 minutes in the low-fibrinogen group and 110 ± 54 minutes in the high-fibrinogen group (p < 0.001). A high fibrinogen level occurred in 58% of patients who weighed more than 85 kg and in 25% of patients who weighed 85 kg or less (p < 0.05). No patient who weighed 60 kg or less had a high fibrinogen level. The high-fibrinogen group also had a greater incidence of a high anti-SK antibody titer: 8 of 13 patients (62%) tested, compared with none of the 8 patients tested in the low-fibrinogen group (p < 0.01). Our data indicate that a high residual fibrinogen level after administration of i.v. SK identifies patients in whom SK is relatively ineffective, probably because of inadequate dosage or inactivation of the drug. Because 30 % of patients in our study had a high residual fibrinogen level after receiving 750,000 IU of SK, our data suggest that the dose of i.v. SK in patients (especially obese patients) with acute myocardial infarction should be substantially more than 750,000 IU.