In a prospective pilot study, 32 patients with advanced inoperable squamous cell carcinoma of the head and neck were treated with polychemotherapy and hyaluronidase combined with radiation therapy. Polychemotherapy consisted of 5 mg vindesine on day 1 and 80 mg/m2 cisplatin on day 2. The patients were given 200,000 IU hyaluronidase intravenously 20 minutes prior to vindesine and cisplatin. Radiation in fractions of 2 Gy per day was administered on the following days (days 3-5, 8-12, 15-18), that is, 12 times. This regimen was repeated twice starting with day 22 and 43. Side effects were mainly of local character: moderate to severe mucositis in 10 patients and mild mucositis in 22 patients. No severe systemic toxicity was observed. Complete remission was achieved in 27 of 32 patients. At present, 16 patients are alive and without relapse. The average time of follow-up is 47 months (range: 26-75 months). These preliminary results suggest that combined therapy with vindesine, cisplatin, hyaluronidase, and radiation are well tolerated by most patients and highly effective against advanced squamous cell cancer of the head and the neck.