From October 1989 to February 1992, 74 patients with mediastinoscopically staged IIIA (N2) non-small-cell lung cancer from 30 CALGB-affiliated hospitals received two cycles of preresectional cisplatin and vinblastine chemotherapy. Patients with responsive or stable disease underwent standardized surgical resection and radical lymphadenectomy. Patients who underwent resection received sequential adjuvant therapy with two cycles of cisplatin and vinblastine, followed by thoracic irradiation (54 Gy after complete resection and 59.4 Gy after incomplete resection or no resection at 1.8 Gy per fraction). There were no radiographic complete responses to the neoadjuvant chemotherapy, although 65 (88%) patients had either a response or no disease progression. During induction chemotherapy, disease progressed in seven patients (9%). Sixty-three patients (86%) had exploratory thoracotomy, and 46 of those (75%) had resectable lesions. A complete surgical resection was accomplished in 23 patients, and 23 patients had an incomplete resection with either a diseased margin or diseased highest node resected. Operative mortality was 3.2% (2/63). In 10 patients (22% of the 46 having resection) the disease was pathologically downstaged. There was no correlation between radiographic response to the induction chemotherapy and downstaging at surgical resection. The full protocol was completed by 33 patients (45% of original cohort). Overall survival at 3 years was 23%. Patients undergoing resection had significantly improved survival at 3 years compared with patients not having resection: 46% for complete resection (median 20.9 months), 25% for incomplete resection (median 17.8 months), and 0% for no resection (median 8.5 months). Five deaths occurred during the treatment period. A total of 18 of the 46 (39%) patients who underwent resection are either alive and disease-free or have died without recurrence.