Four neonates suffered caval thrombosis secondary to indwelling central catheters. Dissolution of thrombus with recombinant tissue plasminogen activator (rt-PA) as a low-dose infusion (0.05 mg/kg/hr) directly into thrombus was successful in three patients. rt-PA was ceased after three days in the fourth patient because of catheter malposition. Thrombolysis was achieved between four and ten days. Rethrombosis occurred in one patient despite heparin prophylaxis. Plasminogen activator infusions were titrated to maintain fibrinogen levels above 100 mg/dl. One neonate suffered an intracranial haemorrhage. Regional rt-PA is an alternative to thrombectomy in critically ill neonates.