BACKGROUND: To determine the potential activity and tolerability of sequential treatment in head and neck cancer, we conducted a phase II trial based on induction chemotherapy of two cycles of taxotere, cisplatin and 5-fluorouracil followed by radiotherapy plus weekly cetuximab. PATIENTS AND METHODS: Thirty-six patients with stage III or IV squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx were treated and evaluated for response and acute toxicity. RESULTS: Eighty-one percent of patients had stage IV disease and 42% had hypopharyngeal and oral cavity primaries. The overall response rate was 81.8%, with 60.6% complete response and 33.3% partial response. Severe toxicities were febrile neutropenia (6%) during induction chemotherapy and dermatitis (48%), mucositis (33%) and dysphagia (12%) during the concurrent phase. CONCLUSION: Our protocol proved to be feasible, effective and well tolerated. This sequential strategy should be further investigated.