An acute obstruction is a life-threatening complication of mechanical valve prostheses, and is caused by the formation of fresh clot or fibrous tissue overgrowth, or both. Accurate selection of the most appropriate treatment for a particular patient is mandatory. From January 1991 to July 1992, 28 cases of prosthetic thrombosis were managed. Twenty patients underwent surgical treatment, with one operative death, and 8 patients were treated with thrombolysis using recombinant tissue-type plasminogen activator (rt-PA). The criteria for using thrombolysis were (1) the recent onset of symptoms, (2) transesophageal echocardiographic evidence of clots on the valve or cardiac chambers, and (3) preserved disc excursions. All patients who underwent thrombolysis had mechanical valves (two bileaflets, four tilting discs, and two ball valves); seven valves were in the mitral position and one was in the aortic. Symptoms of obstruction consisted of cardiac failure in 6 cases or thromboembolism in 5, or both. The mean interval between the onset of symptoms and the initiation of thrombolysis was 81 +/- 65 hours. After infusion of the rt-PA, normal valve function was restored in all patients, as documented by transesophageal echocardiography. No deaths or neurologic complications occurred; there was one episode of minor peripheral embolism. Thrombolysis using rt-PA may be the appropriate treatment in patients with primary thrombosis of mechanical valves, thereby avoiding the operation-related risks.