In a series of three consecutive pilot studies carried out between 1977 and 1981 at Wayne State University, Detroit, Michigan, designed to test the feasibility of multimodality therapy in patients with previously untreated advanced squamous cell carcinoma of the head and neck, patients received three different induction chemotherapy regimens: cisplatin + Oncovin (vincristine) + bleomycin (COB) for two courses; 96-hour 5-fluorouracil (5-FU) infusion and cisplatin for two courses, or 120-hour 5-FU infusion + cisplatin for three courses. Over-all response rates (complete response + partial response) to each of the three induction chemotherapy regimens were high: 80%, 88%, and 93%, respectively. Superior complete response rate in the group receiving three courses of 120-hour 5-FU infusion + cisplatin was 54% versus 29% for COB and 19% for two-course 96-hour 5-FU infusion + cisplatin (P = 0.04). Significant survival advantage at 18 months minimum follow-up for the group receiving three courses of 120-hour 5-FU + cisplatin induction therapy was found. Actual I' and N stage may influence the clinical complete response rate. Responders to initial chemotherapy have significantly better survival as compared to nonresponders regardless of subsequent surgery and/or radiotherapy. These studies show that a multimodality approach to management of advanced head and neck cancer is feasible. Superior complete response rate and survival in one of the treatment groups suggest that choice of induction chemotherapy regimens and/or number of courses is of prime importance in such multimodality treatment programs.