The case is presented of a 35-year-old woman with major thrombotic obstruction of a 29-mm St. Jude Medical mitral valve prosthesis. The thrombi were treated with successive intravenous fibrinolysis under transesophageal echocardiographic guidance, without complication. One large and obstructive thrombus with a long and mobile component, and other smaller and mobile thrombi were detected. These were gradually lysed after two successive administrations of streptokinase (1.5 x 10(6) units over 24 h), and one session of recombinant tissue type plasminogen inhibitor (100 mg over 6 h).