Increased risk of central venous line thrombosis in tiny premature infants occurs because the size of the catheter relative to the cross-sectional area of the vessel is large, decreased plasma levels of plasminogen and antithrombin III, and relative low flow of the infusate through the catheter, in comparison with larger infants. A potentially fatal complication of central venous catheters is an intracardiac thrombus. The yield of detecting right atrial thrombi by routine echocardiographic monitoring is very low. Persistent positive blood cultures in infants with central venous lines, in spite of appropriate antibiotic therapy, or signs of catheter occlusion, may increase the yield of echocardiographic detection of intracardiac thrombi. Surgical removal of intracardiac thrombi in infants weighing less than 1500 gm carries a high mortality rate because of the need to use cardiopulmonary bypass with total circulatory arrest and profound hypothermia during surgery. It is in these infants that thrombolysis with urokinase should be considered. A successful therapy with urokinase of a complete occlusion of the right pulmonary artery by an embolus originating from the right atrium is described in a premature infant. For thrombolysis, a loading dose of urokinase of 4400 U/kg followed by 4400 to 8800 U/kg/hr for a few days was used. The thrombolytic effect was manifested by decreased thrombus echogenicity followed by its disappearance, by increased fibrinogen split products, and by decreased plasma fibrinogen. Urokinase therapy may cause massive bleeding, dislodge an intracardiac thrombus causing obstruction of cardiac valves or main vessels or causing embolization to the pulmonary or systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)