From 1979 to 1980, 52 patients with Stage III-IV squamous cell carcinoma of the head and neck were included in a prospective randomized study on hyperfractionated radiotherapy with or without misonidazole. The radiotherapeutic schedule consisted of two weeks of treatment split by a rest-period of one month, 6 X 1.1 Gy fractions per day for 5 consecutive days (total dose: 2 X 33 Gy/30 f/5 d). Total dose of misonidazole was 12 g/m2 administered daily in 1.2 g/m2 fractions. The overall tolerance of misonidazole was good, with a neuropathy rate of 5.7%. Local control, recurrence and 3 year survival rates did not statistically differ between the two groups. The randomized trials published at the present time, including our own, suggest that misonidazole has no beneficial effect with classical, concentrated or multiple fractions per day radiotherapy.