Because of the low incidence of pulmonary embolism in children, the therapeutic approach is extrapolated from guidelines for adults. An adolescent boy with a massive pulmonary embolism associated with protein S deficiency was cared for successfully with intravenous thrombolytic therapy using 1.3 mg/kg of rt-PA with a 2-hour infusion time. In the absence of contraindications, most physicians consider using thrombolytic drugs in hemodynamically unstable patients who have a pulmonary embolism. A recent study described a subset of hemodynamically stable patients with right-ventricular dysfunction who also might benefit from thrombolytic therapy.