Twenty-nine of 32 patients with advanced squamous cell carcinoma of the head and neck were treated with two courses of an intensive chemotherapy regimen consisting of cisplatin, bleomycin, and methotrexate (PBM). The frequency of toxic effects (in 29 evaluable patients) associated with this regimen was low. Serious neutropenia occurred in 17% and thrombocytopenia in 10% of the courses. Nausea (50%) and severe vomiting (6%) were easily managed. All 26 (100%) evaluable patients with squamous cell carcinoma had significant reduction (less than 50%) of measurable tumor. Complete regression was noted in seven patients (27%). Fifteen patients were treated with PBM prior to receiving radiation therapy or surgery as definitive treatment for their disease. Antitumor response in these patients was rapid, occurring within 3 weeks from the initiation of chemotherapy. Maximal antitumor effect was achieved by Week 6 of induction chemotherapy. No patient showed tumor regrowth prior to the institution of radiation therapy or surgery. Twelve patients with recurrent disease following previous radiotherapy and/or surgery also received PBM chemotherapy. In our study, previous radiotherapy or surgery did not diminish the antitumor effect of PBM, but toxicity was more severe.