IV streptokinase was infused to test the potential reversibility of adult respiratory distress syndrome (ARDS) associated pulmonary vascular thrombosis in five patients suffering from severe ARDS with elevated mean pulmonary artery pressure, increased pulmonary vascular resistance, and angiographically documented pulmonary vascular thrombosis. At 48 hr there was clearance of obstructions in arteries larger than 1 mm in diameter in all patients, increased filling of the microvasculature and small arteries less than 1 mm in diameter in four patients, a fall in pulmonary vascular resistance in all patients, a rise in cardiac output in four patients, improved oxygenation (PAO2/FlO2) in three patients, and variable changes in shunt fraction and ventilator pressures. Expressed as a mean fraction of the preinfusion controls, the postinfusion physiologic values were pulmonary artery pressure = 0.89 mm Hg, pulmonary vascular resistance = 0.68 mm Hg X min/L, cardiac output = 1.36 L/min, central venous pressure = 0.77 cm H2O, pulmonary capillary wedge pressure = 0.92 mm Hg, PAO2/FlO2 = 1.08, and shunt fraction = 0.95. Follow-up angiography showed no evidence of reocclusion. Postmortem studies of the three nonsurvivors confirmed recanalization of thrombosed pulmonary arteries. One documented bleeding episode occurred. We conclude that fibrinolytic infusion can lyse thrombi and possibly improve hemodynamics and oxygenation in ARDS-associated pulmonary vascular thrombosis.