Fifty-one patients with locally advanced squamous cancer of the head and neck (SCHN) were treated with up to three cycles of very-high-dose cisplatin, 187.5 mg/m2 (administered over five days) in hypertonic saline, and bleomycin infusion, 60 U/m2 (administered over five days), prior to definitive local therapy, in an attempt to improve complete remission (CR) and overall response rates. After chemotherapy, patients underwent surgery if the tumor was resectable for cure, (unless the operation involved total laryngectomy), and/or locoregional radiation therapy. Twelve patients (24%) achieved CR and 23 (45%) partial remission (PR) for an overall response rate of 69%. Thirty-nine of the 51 patients are evaluable following chemotherapy and locoregional treatment, and 28 (72%) have achieved disease-free status. Seven of these 28 (25%) have subsequently relapsed. Eleven of the 51 patients (22%) have died at median follow-up of 10+ months (3+ to 24+). Nausea and vomiting (94%) was the most severe acute toxicity. Myelosuppression was mild and nephrotoxicity was effectively prevented by the 3% saline diuresis. Bleomycin was withheld in 12 of 49 (24%) because of deterioration in pulmonary function tests. Ototoxicity in 12 of 49 (25%) and neurotoxicity in 19 of 49 (39%) were the most significant long-term toxicities. Very-high-dose cisplatin and bleomycin in this study was an effective chemotherapy regimen, but not more so than more conventional doses of cisplatin. Toxicity from both drugs was significant.