Patients with advanced carcinomas of the hypopharynx or upper esophagus have among the worst prognoses in head and neck oncology. We developed a treatment regimen of rapidly alternating multi-agent chemotherapy and accelerated interrupted radiotherapy as follows: Three cycles of chemotherapy were delivered [day 1, cisplatin 100 mg/m2; days 1-4, 5-fluorouracil (5-Fu) 900 mg/m2] and repeated every 3 weeks. On day 8 of each chemotherapy cycle radiotherapy was started, consisting of 10 fractions of 200 cGy delivered twice daily, for 5 days. The total dose of radiotherapy was 6,000 cGy over 7 weeks, and the total duration of chemotherapy and radiotherapy was 8 weeks. Nineteen patients with locally advanced, epidermoid carcinoma of the hypopharynx (9 patients) or upper esophagus (10 patients) were treated on this protocol. Minimum follow-up was 1 year. Twelve patients had tumors judged technically unresectable, whereas 7 had tumors considered resectable only with total laryngectomy, which was unacceptable to the patients. One patient died of nadir sepsis during treatment, but otherwise the acute toxicity was relatively mild (grade I/II in 16 patients, grade III/IV in 3 patients). The complete response rate was 83% (15 of 18 patients), and the partial response rate was 17% (3 of 18). No patient failed to respond. The survival rate was 80% at 1 year and 73% at 18 months. At 1 year, 89% of the patients remained in remission and at 18 months, 74% Late complications occurred in 4 patients. These included laryngeal necrosis, pneumonitis, esophageal stricture, and tracheoesophageal fistula.(ABSTRACT TRUNCATED AT 250 WORDS)