The combination of cisplatin and 96-hour infusion of 5-fluorouracil (5-FU) was evaluated in 30 patients with recurrent (local and regional) and disseminated histologically proven epidermoid cancer of the head and neck who failed surgery and radiotherapy. Cisplatin 100 mg/M2 intravenous (IV) bolus was given on day 1 with hydration and mannitol diuresis; 5-FU 1000 mg/M2 per day for 96-hour infusion was started immediately after cisplatin on day 1. All patients had measurable lesions. Eight (27%) patients achieved complete response (CR), and 13 (43%) had partial response (PR). Overall response rate was 70% (8 of 30 CR and 13 of 30 PR). Response rate in patients with recurrent local and regional disease was 89% (17/19) with median survival of 32 weeks, while response in patients with disseminated disease was 36% (4/11) with median survival of 24 weeks. Patients with good performance status (PS) (greater than or equal to 70%) had a response rate of 79% (19/24), while those with poor PS (less than 70%) had a response rate of 33% (2/6). Seven patients with recurrent disease who had a response to this chemotherapy went to further salvage surgical procedures. It is concluded that the combination of cisplatin and 5-FU is very effective and well tolerated in these patients, and leads to further salvage in some patients with improved longevity and quality of life.