Between February 1976 and June 1977, 15 patients with advanced inoperable squamous cell carcinoma of the head and neck were entered in a pilot study sponsored by the Radiation Therapy Oncology Group using combined radiotherapy and multidrug chemotherapy. Chemotherapy consisted of cyclophosphamide, vincristine, and bleomycin (during radiotherapy) and cyclophosphamide, methotrexate, and bleomycin (after radiotherapy). At the time of last followup or of death, the disease had been controlled at the primary site in eight of the 15 patients (53%), in the neck in 12 patients (80%), and in all sites in seven patients (47%). Followup time ranged from 2 to 24+ months with a median of 7 months. Acute toxic effects of the combined treatment, primarily enhanced radiation mucositis and infection, were severe, and three patients had fatal complications. Although the combination chemotherapy may have enhanced the tumor response to radiotherapy in some of these patients, treatment morbidity and complications were prohibitive for the treatment program to progress to a randomized trial.