The aim of the present study, which included 24 pretreated patients (both with radiotherapy and/or cisplatin-containing chemotherapy) with histological grade I/II head and neck cancer, was to investigate whether the enhancing action of cytosine arabinoside on cisplatin antitumor activity might be evidenced without excessive hematological toxicity with the administration of short infusional high-dose cytosine arabinoside, applied before cisplatin. Cytosine arabinoside was administered on day 1 of the treatment cycle at 0h and 12h at the dosage of 500 mg/m2 (1 hour infusion), and cisplatin at 6h and 18h of the same day with a dose of 20 mg/m2. On days 2, 3 and 4, only cisplatin 30 mg/m2/24h was administered. 19 patients were evaluable for activity including 14 patients pretreated with cisplatin-containing chemotherapy. 2/19 achieved complete response (CR), 2/19 a partial response (PR), 8/19 had stable disease and 7/19 progressive disease. Objective responses (2 CR and 1 PR) were evidenced in 3/14 patients previously resistant to cisplatin at the same dosage as in the present regimen. WHO grade IV toxicity for granulocytes was recorded in only one patient.