Before cisplatin-based chemotherapy, long-term survival after resection of primary mediastinal nonseminomatous germ cell tumors was unusual. We reviewed the case histories of 48 patients who underwent multimodality treatment for mediastinal nonseminomatous germ cell tumor between 1976 and 1988. Twenty-eight patients received initial therapy at Indiana University and 20 were referred after having had unsuccessful initial therapy elsewhere. In 44 patients (92%) the levels of either one or both serum tumor markers were elevated at the time of diagnosis. Five patients had choriocarcinoma, three embryonal carcinoma, 12 yolk sac carcinoma, four teratocarcinoma, 22 mixed cell type, and two had an unclassified type. Twenty-two of the 28 patients in our initial therapy group had a complete response to treatment, as defined by normal serum tumor markers and absence of residual tumor. In this group, 16 patients had resection of residual disease after chemotherapy, four had total or near total resection before chemotherapy, and only two had chemotherapy alone. Seventeen patients are surviving after this treatment with a median survival of 64 months and a 57% 5-year Kaplan-Meier survival rate. Only two of the 20 patients who were referred for salvage chemotherapy had a complete response. Both required resection of residual disease after salvage chemotherapy. Only one patient survived after this treatment. There was no significant treatment morbidity or mortality. A multimodality approach to primary mediastinal nonseminomatous germ cell tumor with intensive cisplatin-based chemotherapy, emphasis on normalizing serum tumor markers, and aggressive resection of residual disease now offers survival to a significant number of patients.