We treated 27 patients with regionally advanced non-small-cell lung cancer (NSCLC) with two cycles of neoadjuvant chemotherapy with etoposide, vindesine, and cisplatin. Twenty-three patients were evaluable for response; 13 had a partial response while ten patients had stable disease or disease progression. Subsequent local therapy consisted of surgery followed by radiotherapy in four patients and of radiotherapy alone in 14 patients. Five patients did not receive local therapy. At completion of local therapy, seven patients were considered free of disease including all four who had undergone surgery. Median time to disease progression for the 13 patients who had a partial response to neoadjuvant chemotherapy was eight months (three to 51+ months). The median survival for all patients registered on study was eight months (three days to 53+ months). Chemotherapy induced toxicities included moderate myelosuppression, nausea and vomiting in all patients, and occasional ototoxicity, neurotoxicity, and wasting syndrome. One patient died of intracerebral hemorrhage due to thrombocytopenia. This trial shows that administration of neoadjuvant chemotherapy to patients with locoregionally advanced NSCLC is feasible and may yield an increased response rate compared to patients with stage IV disease. While no clearly beneficial effect of the use of chemotherapy on patient survival is apparent in this study, further studies utilizing neoadjuvant chemotherapy in patients with NSCLC are warranted and should attempt to identify more active combinations of drugs.