Although heparin is often given as an adjunct to tissue plasminogen activator (t-PA), the effect of heparin on t-PA induced fibrin(ogen)olysis is controversial. To address this controversy, we examined the effects of standard and low molecular weight heparin (enoxaparine) on both t-PA induced clot lysis and t-PA mediated fibrinogenolysis in a human plasma system. Accordingly, 125I-labeled fibrin clots were incubated in t-PA containing citrated plasma in the presence or absence of these glycosaminoglycans, and the extent of thrombolysis was determined by measuring residual radioactivity of the clots, while Bβ1-42 levels were used as a specific index of fibrinogenolysis. Over a wide range of t-PA concentrations (0.1 to 1.6 μg/ml), neither heparin nor enoxaparine influences either t-PA induced clot lysis or t-PA mediated Bβ1-42 generation. These findings suggest that either agent could be used as an adjunct to t-PA without compromising either the thrombolytic potential of t-PA or its clot-selectivity.