We have determined the plasma level of fibrinopeptide A as a specific index of thrombin activity during the infusion of a thrombolytic agent in patients with acute myocardial infarction. Peripheral venous plasma levels of fibrinopeptide A increased following the initiation of thrombolytic therapy from 2.7 nmol/L to a peak of 13.0 nmol/L at 30 minutes with streptokinase and from 1.1 nmol/L to a peak of 10.7 nmol/L at 90 minutes with tissue plasminogen activator. The amount of fibrinogen converted to fibrin I was determined by integration of the plasma level of fibrinopeptide A over time. The amount of fibrin I formed over the five-hour period from the start of drug infusion was approximately 10 mg/dL in response to either streptokinase or recombinant tissue plasminogen activator. We conclude that activation of coagulation occurs in response to thrombolytic therapy despite heparin administration. This thrombin action, though transient, would be sufficient to cause rethrombosis if localized and incompletely opposed by fibrinolytic activity.