In an attempt to improve the curative potential of surgery, 46 patients with unresectable Stage IIIA (Clinical N2) non-small cell lung cancer received neoadjuvant chemotherapy with cisplatin and etoposide. After 2 or 3 cycles, 45 patients were evaluable for response; the overall response rate was 82% (37/45) with 3 complete and 34 partial responses. Toxicity was primarily hematologic. Surgical exploration was performed on 35 patients, but resection was possible in only 33 (73%). Of these, 28 resections were complete (62%). Four patients (2CR, 2PR; 9%) had no tumor in biopsy specimen. Three deaths were surgery-related. Median survival of the entire 46 patients was 24.5 months with a 2-year survival of 53%. Cisplatin and etoposide is an effective chemotherapeutic regimen for regionally advanced non-small cell lung cancer; the resection and survival rates justify further trials to compare this approach to other treatment modalities.