Thrombotic vascular occlusion may complicate the clinical course of many neonatal and pediatric pathologic processes. Systemic thrombolytic therapy with heparin, urokinase, or streptokinase may not be appropriate in the critically ill neonate because these agents generate a diffuse coagulopathic state. Direct surgical intervention for repair may be precluded by the small size of the vessels involved. Recombinant tissue plasminogen activator (rTPA) induces only a minimal proteolytic state while inducing thrombolysis within the local environment of the clot. We report our experience with regional rTPA infusion in four critically ill patients with venous and arterial thrombotic disorders. there were two brachial artery occlusive lesions--a neonate with iatrogenic occlusion due to a misplaced intravenous catheter and a 2-year-old child with inadvertent arterial ligation during an attempted venous cutdown. Two venous lesions consisted of a full-term neonate with renal vein/inferior vena caval thrombosis and a 32-week infant with partial superior vena caval thrombosis due to a Broviac catheter. Systemic thrombolytic therapy was contraindicated in these patients because of underlying illnesses. Pretherapy vascular evaluation included Doppler examination and angiography. The rTPA infusion was continued until there was evidence of clot lysis by ultrasound, angiogram, or venogram. Infusion rate of rTPA was adjusted according to fibrinogen levels. All three neonates responded successfully to rTPA therapy. Two neonates required only bolus administration and one responded to combined bolus and continuous infusion therapy after 58 hours. rTPA failed to reverse brachial artery occlusion in the 2-year-old child with purpura fulminans.(ABSTRACT TRUNCATED AT 250 WORDS)