Thrombosis of the central venous system (CVT) occurs in 20% to 30% of patients with indwelling catheters. This complication is usually treated with anticoagulation, extremity elevation, and catheter removal. Thirty-eight patients with CVT at our institution were treated with thrombolytic therapy to rapidly resolve symptoms and avoid removal of the catheters. Complete clot lysis occurred in 36 of 38 patients (95%) within 1 to 5 days (mean: 2.4 days). Symptoms resolved with clot resolution. Thrombolytic therapy detected stenoses in 22 patients. Angioplasty was successful in 64% of these patients. Five catheters were removed. Complications occurred in six patients: nonfatal pulmonary embolus, three bleeding episodes, pain with infusion of urokinase, and an episode of septic phlebitis. This experience suggests that thrombolytic therapy is safe, rapidly resolves symptoms of thrombosis, uncovers anatomic abnormalities amenable to angioplasty, and allows central venous catheters to remain in place despite central venous thrombosis.