BACKGROUND--Aortic thrombosis is more frequent since the use of umbilical artery catheters in neonatal intensive care units. Some drugs or surgery are proposed to prevent complications; experience with tissue plasminogen activator (tPA) is still limited. CASE REPORT NO 1--A neonate, weighing 2400 g, developed respiratory distress requiring insertion of a catheter into her umbilical artery at H12. Ultrasonography on day 3 showed aortic thrombosis extending to the right renal artery which was confirmed by angiography. tPA 0.1 mg/kg was administered through the catheter, followed by 0.3 mg/kg/h for 3 hours and heparin, 100 IU/kg/hour for 54 hours. Angiography, performed 18 hours later, showed complete disappearance of the thrombosis. CASE REPORT NO 2--A neonate, weighing 2520 g suffered at 12 hours of life from seizures, apnea and bradycardia which required insertion of a catheter into her umbilical artery. Cyanosis of the right leg with weakening of femoral pulsations, 14 hours later, lead to the diagnosis of aortic thrombosis which was confirmed by aortography. The patient was given tPA 0.1 mg/kg followed by 0.3 mg/kg/h for 3 hours and heparin 100 IU/kg/hour for 6 hours. Amplitude of femoral pulsations strikingly increased within 6 hours with the disappearance of cyanosis. CONCLUSION--These results suggest that tPA can be useful in neonates presenting with aortic thrombosis.