Although there is no definite survival advantage to the use of sequential induction chemotherapy (CT) followed by radiotherapy (RT) in advanced resectable laryngeal cancer, this approach does succeed in preserving the larynx in many of these patients. The authors performed this study to analyze their results using a similar approach for patients with advanced resectable cancer located outside the larynx who would have required a total laryngectomy for oncologic or functional reasons. A retrospective study was performed at a single institution that included all patients with advanced resectable nonlaryngeal head and neck cancer treated with induction CT between January 1990 and August 1995. A total of 19 patients were included, with primary cancers located in the oropharynx in 14 patients, the hypopharynx in four, and the oral cavity and oropharynx in one. Eight patients had clinical stage III disease, and 11 patients had stage IV disease. Our treatment protocol consisted of two cycles of induction CT with cisplatin and 5-fluorouracil, followed by a third cycle of CT and subsequent RT in patients who achieved at least a clinical partial response (PR) after two courses of induction CT. Eighteen of 19 patients were evaluable for response. Overall, 13 patients (72%) had a major response (PR or CR) to induction CT at the primary site, and eight patients (57%) had a major response to chemotherapy in the neck. With a mean follow-up of 53 months (range, 24-71 months), the disease-specific survival was 57% for those patients with cancer of the oropharynx and oral cavity. In the subset of patients with hypopharynx cancer, 3 of 4 patients died of cancer despite achieving major response to induction CT. Organ preservation using sequential CT and RT for advanced resectable nonlaryngeal head and neck cancer is feasible, and the results in our experience with cancer of the oropharynx were similar to those reported for primary laryngeal cancer. Our limited experience using this protocol for cancer of the hypopharynx has been disappointing.