In patients with non-resectable carcinoma of the head and neck, radiotherapy produces an average survival of 12 months. Neoadjuvant chemotherapy followed by radiotherapy has been shown to prolong survival and preserve organ structure and function, and to reduce systemic relapses in patients with advanced, resectable disease. An analysis was made of 35 patients treated with sequential chemotherapy and radiotherapy, 20 with non-resectable disease and 15 with resectable disease who refused surgery. Treatment consisted of 4 cycles of cisplatin + 5-fluoruracil in a 96-h continuous intravenous infusion in 16 patients, and the same treatment with leucovorin in 19 patients. After chemotherapy, the patients underwent cobalt irradiation of the primary tumor and neck. Chemotherapy produced a complete response rate of 46% and a partial response rate of 28%, yielding an overall rate of 74%. After radiotherapy, the CR increased to 63%. After 92 months of maximum follow-up, overall survival was 20% and median survival was 25 months. Locoregional relapses were the main cause of treatment failure. Our results suggest that sequential chemo-radiotherapy achieved encouraging CR rates with no significant increase in toxicity, prolonged survival in non-resectable patients, and enabled organ preservation in patients with resectable disease.