We have combined cisplatin, 5-fluorouracil infusion, and radiation in an every-other-week schedule in a phase I-II study of 44 patients with head and neck cancer to assess toxicity and response. Ten patients were treated palliatively with 2 to 6 cycles of therapy, and 34 were treated curatively with a planned 7 cycles. Of 34 patients treated curatively, all were initially controlled. Three died during treatment (1 myocardial infarction, 1 bowel perforation, and 1 renal failure after amino-glycoside antibiotics). Four patients have had regional recurrences, 7 failed at distant sites (follow-up 2 to 5 yr). Thirty-three percent of 20 patients with complete clinical disappearance of all evidence of their cancer have had a recurrence, as have 38% of 14 (P greater than .1) with some residual abnormalities (partial responders) following treatment. All failures were in the 25 patients with T4 and/or N3 disease. None of the 9 patients with lesser stage IV or stage III disease who were followed for 24 months or more had recurrences. Eighteen patients (53%) survive with a projected 3-year survival of 63% (95% confidence interval 47% to 77%). Nine (27%) have died of disease, 1 (3%) died of a second primary in the head and neck, 3 (9%) of intercurrent disease at 15 to 45 months, and 3 (9%) during treatment. Of the 10 patients treated palliatively, 1 died during treatment with hepatic failure, 6 had complete responses, and 2 had partial responses.(ABSTRACT TRUNCATED AT 250 WORDS)