Since thromboembolic events (TE) are rare among children there is only limited information on the optimal choice of antithrombotic agents, dose and duration of antithrombotic therapy. Recombinant tissue plasminogen activator (rt-PA) is increasingly used for thrombolytic therapy of organ- and limb threatening thrombosis in children. We investigated retrospectively the efficacy and safety of rt-PA in 13 children treated consecutively between 1996-1999, following the same protocol. The median age was 3.9 years (3 days to 16 years). All children suffered from underlying diseases. In addition, 7 children had cardiac catheters and central venous catheters and two children suffered from Factor V Leiden mutation. Seven children presented with a TE in the arterial system, 6 with one in the venous system. All children were treated with continuous infusion of rt-PA (median dose 0.05; 0.0125-0.2 mg/kg/h) together with low-dose standard heparin (median dose 8; 5-15 IU/kg/h). Thrombolysis was performed for a median time period of 102 hours (6 hours to 16 days). Treatment effects on the thrombus were regularly confirmed by ultrasound. Plasma levels of fibrinogen and haemoglobin decreased moderately during treatment. No cumulative effect or increased dose requirement of rt-PA was detected during extended treatment. Patency of obstructed vessels was achieved in all children. One child developed severe gastrointestinal bleeding. Six children (46%) developed minor bleeding at the site of catheter puncture. One child developed rethrombosis at the site of the previous thrombus 2 weeks after completion of rt-PA treatment. Under rigorous laboratory and ultrasound control, our protocol using low dose rt-PA over a prolonged period of time was effective and safe.