The results of hexamethylmelamine therapy in 20 patients with advanced squamous cell head and neck cancer are reported. No patient had previously received chemotherapy. The dose of hexamethylmelamine was 8 mg/kg/day p.o. There was partial response in 3/20 (15%) patients. The duration of the response was 6-10 weeks. Twelve of 20 (12/20) patients had stable disease for a median of 8 weeks (range: 4-18 weeks). Hexamethylmelamine was well tolerated with the only significant toxicity being mild nausea and vomiting. This drug deserves further evaluation in the treatment of head and neck cancer.