Combining accelerated radiotherapy with carbogen and nicotinamide (NAM) has been proposed as a strategy to overcome the sparing effect of tumour clonogen repopulation and hypoxia. Six patients with squamous cell carcinomas of the head and neck were given accelerated radiotherapy, carbogen breathing and high dose nicotinamide in order to evaluate the feasibility of this treatment regimen. The patients received radiotherapy in two daily fractions of 1.8-1.9 Gy, five days/week, total dose 54-57.6 Gy, in an overall treatment time of 19-22 days. The interfraction intervals were 7-8 hours between the two fractions on the same day. Carbogen breathing was started 5 minutes before and went on during each radiation fraction. a variety of NAM doses were administered orally in conjunction with radiation therapy and analyses of plasma concentrations of NAM and its metabolites were performed. The most common side-effect from NAM was nausea and vomiting, which in one case hampered further NAM administration. The side effects were not related to plasma levels of NAM or its main metabolites. Additionally, one patient with preexisting heart disease developed a severe hypotension and renal dysfunction. All acute reactions healed without further complications. The mucosal reactions were generally brisk. Thus, the combination of accelerated radiotherapy with carbogen and NAM seems to be tolerable.