Twenty-two of 53 (42%) patients developed subclavian vein thrombosis (SVT) while receiving chemotherapy for advanced malignancy by an ambulatory pump constant infusion delivery system. The median time to thrombosis was 30 days (range, 5-270 days). Seven patients (36%) were asymptomatic and received no specific anticoagulation. Twelve patients (50%) received heparin followed by coumadin for 2 to 3 months. None of the 19 patients developed complications of the SVT. In three patients (14%), acute SVT progressed to complete or partial superior vena cava syndrome. The use of fibrinolytic therapy was successful in all three patients, and was adequate to lead to complete clinical resolution. Predisposing factors in the patient population included: (1) decreased antithrombin III levels prior to catheter insertion; (2) intrathoracic tumor, possibly creating low flow rates; and (3) improper or suboptimal home management of the catheter. The development of SVT was not related to the chemotherapeutic agent infused or the duration of therapy. The frequency of SVT in this patient population necessitates consideration of prophylactic methods in high-risk patients.