Tissue plasminogen activator (rTPA) has been advocated for the treatment of thromboses in children, however, few reports have addressed the safety and efficacy of this agent in neonates. A retrospective literature review(MEDLINE) through 1995 revealed only 19 neonates in 11 reports to have received this therapy. In 11/19 patients, the clot was arterial in location. In 10/11 patients, the arterial clot was associated with an intra-arterial catheter. Patients received from 0.05-0.7mg/k/hr of rTPA by either intravenous bolus or continuous infusion. Clot resolution was complete in 8/11, partial in 2/11, and rTPA therapy failed in 1/11. Previously, no bleeding complications were reported in neonates treated with rTPA for arterial thromboses. In the present study, we prospectively treated 7 neonates with rTPA from 1993-1995 for arterial thromboses documented by clinical exam and doppler ultrasound. Infants were both term (2/7) and preterm (5/7, 24-36wks) with birth weights ranging from 543 to 3289 grams. The clots were located in the iliac artery(1), aorta (2), axillary artery (1), femoral artery (1), and palmar digital artery (1). Risk factors included arterial catheterization (2), arterial puncture (1), infection (1), and extremity trauma (2). In 3 patients, no risk factors were identified. All infants received rTPA by continuous (PIV) infusion at a median dose of 0.4 mg/k/hr (range 0.1-0.5 mg/k/hr) for a median duration of 26 hours (range 6-38 hr). Clot resolution was complete in 4/7 patients (57%) and partial in 2/7 (28%). One patient failed therapy. Complications included oozing from puncture sites (4/7), hematuria (2/7), pulmonary hemorrhage (1/7), and intraventricular hemorrhage (Grade II-1, Grade IV-1). The most serious bleeding was seen in infants who received high dose rTPA (0.5mg/k/h). Bleeding risk did not correlate with any clotting studies. Two patients died following rTPA therapy. In one, the death was in part attributed to bleeding complications associated with rTPA. Combining the literature review with our own experience indicates that rTPA can be used to successfully treat central and peripheral neonatal arterial thromboses.However, both minor and major bleeding complications are seen with rTPA. Future studies will need to address the safety and efficacy of this agent in comparison with other thrombolytic therapy.