During thrombolytic therapy of myocardial infarction (MI) with urokinase or streptokinase (SK), levels of fibrin(ogen) degradation products in serum are often dramatically elevated as a result of a combination of systemic fibrinogenolysis and local thrombolysis. Others have measured increased levels of D-dimer in serum of MI patients after SK therapy and postulated that thrombolysis could be monitored during SK therapy by measuring D-dimer levels. In the present study rt-PA was infused into healthy volunteers to analyse if elevated FbDP levels in MI patients really reflect coronary thrombolysis or could be due to a systemic effect. Over a period of 60 min., three groups (n = 6 each) were given i.v. 0.23 mg rt-PA/'kg (group I), 0.50 mg rt-PA/kg (group II) and a placebo infusion (group III), respectively. Two blood samples were taken from an anticubital vein in the arm contralateral to the site of infusion (one on citrate/ aprotinin, the other on citrate alone) at different time points. Using a new enzyme immunoassay (EIA), based on monoclonals and development by us, we measured FbDP in plasma (not serum). Before infusion all volunteers had FbDP levels ≪ 0.5µg/ml. Upon infusion FbDP levels in groups I and II increased to average values of 1.0 ± 0.4/µg/ml and 0.8 ± 0.2/µg/ml, respectively, for the samples taken in citrate/aprotinin. The values in citrate alone did not differ significantly, and were 1.1 ± 0.5/µg/ml and 0.8 ± 0.3/µg/ml for groups I and II, respectively. FbDP levels in group III remained ≪ 0.5/µg/ml. The results show that FbDP levels increase upon rt-PA infusion, even in healthy volunteers. This suggests lysis of systemic fibrin. We conclude that lysis of systemic fibrin limits the value of FbDP levels as a measure for coronary thrombolysis.