A multi-institutional National Cancer Institute trial of preoperative cisplatin (100 mg/sq m, day 1) and intravenous bleomycin sulfate (15-mg/sq m bolus, day 3, followed by 15 mg/sq m/day, 24-hour infusion, days 3 to 7) was carried out in patients with previously untreated, resectable stage III and IV squamous cell carcinoma of the oral cavity or larynx and hypopharynx. Of the first 113 patients who received a single course of induction chemotherapy, eight complete responses and 47 partial responses at the primary site were observed (49%). Of 76 patients who had clinically positive regional adenopathy, 11 complete responses and 31 partial responses of neck nodes were observed (55%). The response rates of the primary tumor and the regional nodes to induction chemotherapy were assessed with respect to several pretreatment patient and tumor characteristics and to reported toxic effects after chemotherapy. Of the factors examined, no prognostic indicators were highly useful to predict the response of the primary tumor. However, the response of regional adenopathy was associated with the initial N class, the site of primary tumor, and the response of the primary tumor to induction chemotherapy.