AbstractFrom January 1987 to May 1988, 16 patients with advanced squamous cell carcinoma of the head and neck received combined treatment, based on an alternating schedule of chemotherapy and multiple fractions per day (MFD)‐radiotherapy. The chemotherapy regimen consisted of cisplatin, 20 mg/m2, followed by 5‐fluorouracil (5‐FU), 200 mg/m2i.v. push, from days 1 to 5 during weeks 1, 5, and 9. Radiotherapy was administered in two courses of 32 Gy each (total dose, 64 Gy) during weeks 2 and 3 and 6 and 7. Each course was given in two fractions per day, 5 days per week. The 16 patients were evaluated for toxicity and response. We observed 7 complete responders, 6 partial responders, and 3 nonresponders. The overall response rate was 81%. Toxicity was heavy: 44% of the patients developed grade III‐IV mucositis. Our results suggest that cisplatin and 5‐fluorouracil alternating with MFD‐radiotherapy is effective; however, a new less toxic scheduling must be d