Twenty-seven patients with squamous cell carcinoma of the head and neck were treated with i.v. cisplatin 50-100 mg/m2 followed by a rapid infusion of cytosine arabinoside 500-4,000 mg/m2. All except four of the patients had received prior irradiation and six had had prior chemotherapy. There was one early death. Of 25 evaluable patients, one (4%) achieved a complete remission and 10 (40%) achieved partial remissions lasting 6-50 weeks (median, 16 weeks). Ten patients (40%) were classified as having stable disease, including five (20%) who experienced minor responses lasting 5-8 weeks. Four patients (16%) had progressive disease. Drug doses, patient performance status, and prior exposure to chemotherapy did not appear to alter the response rate. Gastrointestinal toxicity was severe in some patients. Myelosuppression tended to be unpredictable and variable within individual patients and was not clearly related to drug doses. Two patients had generalized seizures and one became confused while hypomagnesemic. Renal toxicity, ototoxicity, and paresthesias were seen only at a cisplatin dose of 100 mg/m2. One patient developed stomatitis and one had an allergic reaction to cisplatin. There was one possible drug-related death. This regimen is reasonably well tolerated and may be somewhat more active than cisplatin alone, although further studies are needed to confirm it. Further studies involving additional doses of high dose cytosine arabinoside following cisplatin could also be worthwhile.