Forty-two patients with advanced head and neck cancer entered this phase II trial of long-term continuous 5-fluorouracil (5-FU) infusion at a dose of 300 mg/m2/day for a maximum of 16 weeks. Objective response rate was 15% in 41 evaluable patients. Median time to progression was 2.9 months, and median survival 4 months. Toxicity was generally mild. Reversible stomatic and hand-foot syndrome WHO grade III-IV was observed in 5 and 3 patients, respectively. Haematologic toxicity and emesis were less pronounced with no grade III-IV toxicity. One patient had to discontinue treatment because of ataxia. No catheter-related toxicity and no treatment-related mortality were observed. In the present study long-term continuous infusion of 5-FU has only modest activity in terms of response rate, but the activity is comparable with other single-agent regimens. The treatment is well tolerated, with minimal toxicity making it usable in a palliative situation.