Desmopressin acetate (DDAVP) is known to stimulate the release of tissue-type plasminogen activator (t-PA) from endothelial cells, but it is unclear whether the increased t-PA actually elicits the plasmin generation and fibrin(ogen)olysis in the circulating blood. We measured plasma levels of plasmin-alpha 2-plasmin inhibitor complex, fibrinogen degradation products (FgDP) and fibrin degradation products (FbDP) following desmopressin infusion in 19 patients with bleeding disorders or thrombophilia. Administration of desmopressin (0.3-0.4 microgram/kg) produced a 4.0-fold increase in plasmin-alpha 2-plasmin inhibitor complex at 30 min, whereas neither FgDP nor FbDP was elevated significantly. These findings indicate that desmopressin infusion provokes the generation of plasmin in vivo, but most of the plasmin generated is complexed to alpha 2-plasmin inhibitor and does not degradate fibrin or fibrinogen.