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Conventional radiotherapy alone in treatment of unresectable or locally advanced head and neck cancer has poor results. To improve outcome without significant increase in acute and late morbidity, we began a moderately accelerated hyperfractionation radiation therapy protocol without breaks for treatment of unresectable/advanced head and neck malignancies. From August 1984 to June 1995, 48 patients with unresectable or advanced carcinoma of the head and neck were treated using a protocol of accelerated hyperfractionation radiation therapy at Kaiser Permanente Medical Center, Los Angeles. Patients were treated twice a day using 150 cGy per fraction, 4 days per week, to a final dose of 60 Gy. Two patients were excluded from this analysis because they did not complete treatment. With a median follow-up of 33 months, 31 (67%) patients have had disease recurrence, 30 (65%) of whom had a locoregional component to their failures. At the last follow-up, 12 patients (26%) were alive with no evidence of disease, 30 patients had died of disease, and 4 had died of intercurrent disease without recurrence. Nine (19%) patients required treatment interruptions averaging 8 days in duration. This accelerated regimen resulted in outcomes similar to those with conventional radiotherapy, most likely because of a conservative total dose. Further refinement of fractionation schedules with potential incorporation of chemotherapy must be investigated.