This protocol was designed to achieve an improvement in the overall and disease-free survival in locally advanced, previously untreated carcinoma of the head and neck. 53 patients (pts) with locally advanced Stages III and IV, MO squamous cell carcinoma of the nasopharynx, larynx, paranasal sinuses, oral cavity, oropharynx, hypopharynx and one of unknown origin were treated with intensive chemotherapy followed shortly thereafter by radiotherapy. Induction chemotherapy consisted of two cycles of cisplatin 100 mg/m 2 over 60 min on day 1, plus 5FU 1000 mg/m 2 continuous infusion over 24 h on days 2–5, with a 10-day interval between the two cycles, followed by definitive radiotherapy after 10 days. The overall response rate to chemotherapy was 79%, with a 28% complete response (CR) rate and a 51% partial response (PR) rate. The overall CR rate after radiotherapy was 70%. With a median follow-up period of 48 months, the 5-year actuarial survival and disease-free survival rates were 67% and 45%, respectively. No difference was found in the survival probability of pts with carcinoma of the nasopharynx, larynx or other primary sites. The survival of pts with a performance status (PS) ≤1 was better than pts with PS>1, 72% versus 51% (not significant). The survival probability of complete responders to chemotherapy was superior than the survival of non-complete responders to chemotherapy, 100% versus 54% [P= 0.001]. The main toxicity was mucositis during radiotherapy. In conclusion, this treatment regimen demonstrated a high CR rate and survival probability in pts with locally advanced and mostly inoperable head and neck cancer.