Seventy patients with squamous-cell carcinoma of the head and neck were treated with a 24-hour infusion of cisplatin, followed by a 5-day continuous infusion of 5-fluorouracil (5-FU). Among 31 patients without prior treatment, stage III (six patients) and IV (25 patients), there were seven complete responses (CRs) and 19 partial responses (PRs) for an overall response rate of 84%. In the group of 30 patients with recurrent disease after surgery and/or radiotherapy, there were five CRs and ten PRs (total response rate of 50%). Among nine patients who failed prior chemotherapy, there were two CRs and one PR. Performance status and stage had minor effects on response frequency. The projected survival in the no prior treatment group was 59% at 22 months while the median survival of the recurrent cancer group was nine months. Compared to our previous study using cisplatin-vincristine-bleomycin (COB) chemotherapy, our present regimen has a higher CR rate (P less than .008). Durations of response and survival in the present study appear to be longer in the unresectable group and the recurrent cancer group. Toxicity was generally mild. The use of dexamethasone, diphenhydramine, droperidol, and perphenazine as antiemetics prophylactically resulted in 28% of treatment cycles associated with vomiting. This compares favorably with our previous 79% incidence of vomiting. This regimen appears to be more effective than our previous regimen and can be given with less toxicity.