A total of 44 patients with previously untreated Stage IV squamous cell carcinomas of the head and neck were treated with a combination of cis-platinum (100 mg/sq m) and 96-hour infusion of 5-fluorouracil (5-FU) (1,000 mg/sq m/day) in two courses or with cis-platinum (100 mg/sq m) and 120-hour infusion of 5-FU (1,000 mg/sq m/day) in three courses. In the 26 patients receiving the two course regimen, the tumor response rate was 88.5%. In five of the 26 patients complete disappearance of the tumor was achieved; partial remission was obtained in 18 of 26 patients. The main side effects were nausea and vomiting (70%), leukopenia (27%), and mild-to-moderate renal toxicity (27%). In the 18 patients who received the three course regimen of 5-FU and cis-platinum, there were 11 (61%) complete responses, 6 (33%) partial responses, and 1 (6%) minimal response. The incidence of complete response was increased with each course given. No added toxicity was observed with surgery or radiotherapy.