Thirty-one patients with unresectable squamous cell carcinoma of the head and neck, 28 with local or distant recurrences following primary surgery and/or radiation and three with distant metastases at diagnosis, were treated with cisplatin and methylglyoxal bis-guanylhydrazone (MGBG). Cisplatin was given at 60 mg/m2 i.v. every 21 days X 3, followed by 80 mg/m2 every 28 days in responding patients. MGBG 500 mg/m2 i.v. was given weekly X 5, then every 14 days. Each dose of MGBG was to be escalated in the absence of toxicity, but in the majority of patients doses greater than 500 mg/m2 resulted in unacceptable toxicity. Gastrointestinal symptoms were the major side effects of this combined treatment. In 28 evaluable patients there were two complete remissions and nine partial remissions. This 39% response rate is not different from that reported with either drug alone. Combined cisplatin and MGBG as administered in this study had no apparent advantage compared to either agent alone in this group of patients.