Treatment strategies for locally advanced nonsmall cell lung cancer have failed to significantly alter the survival of most patients. Treatment strategies utilizing, neoadjuvant chemotherapy and concurrent chemotherapy/radiation therapy have shown promise in some reports. Twenty-six consecutive patients with stage III, non-small cell lung cancer were treated over a 3 year period according to a strategy involving neoadjuvant chemotherapy (mitomycin, vinblastine, cisplatin [MVP]) followed by reassessment for surgical resection, followed by treatment with concomitant radiation therapy and chemotherapy (hydroxyurea [HU], 5-fluorouracil [5-FU]). Staging revealed stage IIIa disease in 15 patients and stage IIIb disease in 11 patients. Nine of 18 evaluable patients responded to MVP (50%) with 1 CR and 8 PRs. Only one of nine responders underwent surgical resection. Eleven of 19 patients receiving concomitant 5-FU, HU, and radiation therapy were evaluable for response. Two of 11 patients were converted to clinical CRs, and the remaining 9 patients had stable disease. Myelosuppression, mucositis and hand-foot syndrome were observed with 5-FU/HU/RT. Median survival for all patients is 10.5 months. One and 2-year survival is estimated at 36% and 27%, respectively. This clinical trial combining neoadjuvant chemotherapy with concurrent chemotherapy/radiation therapy is feasible. Select patients appeared to have a survival benefit however most patients failed to derive an improvement in clinical endpoints.