BACKGROUND Both twice daily fractionated radiotherapy and concurrent cisplatin with once-daily radiotherapy have been shown to improve local disease control in patients with head and neck cancer. The objective of this phase I trial was to determine the maximum tolerated dose of cisplatin which could be given as a continuous infusion concurrent with twice-daily radiotherapy to patients with locally advanced head and neck cancer. METHODS Patients were treated with radiotherapy at doses of 110 cGy twice daily for 5 days per week to a total dose of 7040-7590 cGy. Concurrent with radiotherapy, patients received continuous-infusion cisplatin for 5 days per week. Groups of 3-6 patients were treated with doses of 1-3 mg/m2/day. RESULTS Central nervous system toxicity became dose-limiting. At 1 mg/m2, 2 mg/m2, and 3 mg/m2 confusion was observed and one patient had a seizure. At 3 mg/m2, another patient suffered severe sensory and motor neuropathy. Despite bulky tumors, 12 of the 14 patients had an objective response and 3 achieved a complete response. CONCLUSIONS the combination of twice-daily fractionated radiotherapy and concurrent cisplatin by continuous infusion is severely toxic and achieves results similar to less toxic programs. It is not recommended for further investigation or therapy.