Over-activation of the fibrinolytic system may result in proteolytic destruction of fibrinogen. However, the effect of the degradation products formed during fibrinogenolysis on fibrinolytic process and plasminogen/plasmin properties remains unclear. To investigate this effect and its mechanism, the ability of fibrinogen fragments E and D to act on plasminogen and tPA binding, proenzyme activation, fibrin clot lysis and plasmin inhibition by plasma α2-antiplasmin, were studied. It was found that early product fragment EE binds to plasminogen and tissue-type plasminogen activator and enhances plasminogen conversion into plasmin. C-terminal lysine residues of all 3 chains pair and 16 or 23 amino acid residues of Aα- chain are essential for this process. C-terminal lysines of fragment E Aα- and γ-chains and lysine-binding site of tPA kringle 2 are responsible for the interaction between these proteins. Binding of fragment E to plasminogen is provided by N-terminal Aα1–19 and C-terminal Bβ120–122 regions. Late plasmic fibrinogen degradation product fragment EL loses the ability to potentiate plasmin generation but can bind proenzyme and its activator. Fragment D has no binding properties towards plasminogen and tPA. None of fibrinogen fragments protects plasmin from α2-antiplasmin inhibition. It is concluded that at over-activation of the fibrinolytic system and subsequent fibrinogenolysis, the products of fibrinogen degradation, can bind plasminogen and tPA and potentiate generation of plasmin, which will be neutralized under the normal level of the plasmin inhibitor.