Twelve male patients with mediastinal nonseminomatous germ cell tumors were treated with chemotherapy (with or without operation and radiation therapy) between 1963 and 1980. Eight patients, treated with only chemotherapy and radiotherapy, died with a median survival from diagnosis of 6 months (range, 3 to 12 months). The 4 survivors remain alive at 12, 15, 34, and 56 months from diagnosis; all are without evidence of disease. All surviving patients were treated with surgical resection of disease either before of after chemotherapy. A major problem in the management of mediastinal nonseminomatous germ cell tumors is the persistence of local disease, which may be overcome by vigorous cytoreductive intervention. Multicenter collaboration will be required to define the optimal combined-modality approach.