Between December 1982 and October 1986, 131 patients with stage II-III-IV squamous cell carcinoma of the oropharynx or oral cavity were randomized to induction chemotherapy, consisting of bleomycin (10 mg/m2/day in continuous infusion from day 1 to day 5), methotrexate (120 mg/m2 on day 2) followed by folinic acid, 5-fluorouracil (5 FU) (600 mg/m2 on day 2), and cisplatin (120 mg/m2 on day 4) every 4 weeks for a total of three cycles followed by definitive locoregional treatment versus locoregional treatment alone. The modalities of definitive treatment (radiotherapy +/- surgery) were chosen prior to randomization. A total of 116 patients were evaluable. Of 55 patients in the chemotherapy arm, four (7%) had a complete response (CR) and 23 (42%) a partial response (PR) following the induction regimen. At the completion of locoregional treatment, 76% (42 of 55) of patients in the experimental group were in CR compared to 89% (54 of 61) in the control group. There was no difference in survival, cause-specific survival, and pattern of relapse between both groups. The median survival was 22 months in the chemotherapy group and 29 months in the control group. Responders to chemotherapy did not fare better than nonresponders. Chemotherapy-related toxicities were few and most of them related to cisplatin which was reduced to 100 mg/m2 for 35 patients. There were no treatment-related deaths and, in the experimental arm of the trial, no increased morbidity from locoregional treatment. This induction regimen does not offer any advantages over standard treatment.