Twenty-eight patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) received neoadjuvant chemotherapy with cisplatin (120 mg/m2 on days 1 and 29) and vinblastine (4 mg/m2 weekly for 6 weeks). At the completion of induction chemotherapy, all patients were assessed for resectability. Those patients judged to be resectable underwent thoracotomy. All remaining patients received thoracic radiation therapy (5500 cGy) followed by additional chemotherapy in those patients responding to neoadjuvant treatment. There were 15 partial responses to neoadjuvant chemotherapy for an overall response rate of 54% (95% confidence interval, 36% to 71%). Only five partially responding patients (18%) were thought to have had sufficient tumor regression to allow for a potentially curative resection. However, a complete resection was done in only two patients. Overall median survival was 12 months (range, 4 to 72 months) with 1-year, 2-year, and 3-year survival rates of 54%, 39%, and 11%, respectively. The primary toxicity associated with neoadjuvant chemotherapy was moderate to severe (Eastern Cooperative Oncology Group Grade 3 or 4) nausea and emesis in 25% of patients. Hematologic toxicity was relatively modest; only one patient had Grade 4 leukopenia (less than 1000/microliter). Fever and neutropenia were uncommon, and there were no documented septic episodes or treatment-related deaths. Compared with historic controls treated with radiation therapy alone, cisplatin-based neoadjuvant chemotherapy appeared to improve the median and long-term survival of Stage III NSCLC patients modestly.