Alterations of coagulation and fibrinolysis induced by administration of single or two chains rtPA are detailed from personal and published results. One should differentiate between the thrombolytic activity, responsible for the efficacy of the drug on thrombosis and the systemic fibrinolytic activity, inducing the decrease in fibrinogen and coagulation factors which probably contribute as to the risk of bleeding, mostly related to invasive explorations (arterial punctures, catheters...), but possibly spontaneous. Few assessments are made: a sufficient plasma level of rtPA should be present to obtain a good efficacy; the degree of fibrinogen decrease is variable between individuals, although it is moderate in most patients (80% of cases); results of the measurements of fibrin degradation products are disappointing and do not allow the laboratory diagnosis of thrombus dissolution. Concerning the risk of re-occlusion, a careful monitoring of heparin treatment may reduce this risk but further studies are needed.