The feasibility and early toxicity of radiotherapy with carbogen breathing and nicotinamide was tested in 74 head and neck cancer patients. Forty patients with laryngeal and hypopharyngeal tumors were treated with an accelerated schedule combined with carbogen alone (16) or with carbogen and nicotinamide (24). Thirty-four patients with far advanced unresectable tumors of the oral cavity and oropharynx received conventional radiotherapy with carbogen [16] or with carbogen and nicotinamide (18). Some enhancement of skin reaction was observed with nicotinamide but this remained well within limits of tolerance. With the accelerated regimen there was increased severity of mucosal damage expressed as confluent mucositis in 95% of patients which required healing times of 3-4 months in four patients. Eventually restoration of the mucosal lining was complete in all cases. Nausea and vomiting are the most frequent side effects of nicotinamide and were reported by 60% and 36% of the subjects, respectively. In 26% this was reason to discontinue drug intake. Severe renal dysfunction was associated with nicotinamide intake in two patients of this study and in one other patient who presented later. It is our conclusion that radiotherapy combined with carbogen and nicotinamide is a safe treatment with manageable side effects. We recommend not to give nicotinamide concomitantly with nephrotoxic medication or to patients who have impaired renal function. Preliminary tumor control rates are encouraging and clinical testing will be continued.