Thirty-two patients (only two had previously untreated disease) with squamous cell carcinoma of the head and neck were treated with alternating combination chemotherapy. The regimen consisted of cisplatin (50 mg/m2) and bleomycin (30 units) given iv on Days 1 and 2, alternated with 1 hour of sequential methotrexate (200 mg/m2) and 5-FU (600 mg/m2) given iv, plus oral leucovorin rescue on Day 22. The entire cycle was repeated every 5 weeks (less than or equal to five cycles). Objective tumor regression was obtained in 33% of the 30 evaluable patients, with 13% complete regression. The median duration of response was only 3 months. Evidence of response occurred within one cycle, and was maximal after two cycles. Toxicity was very mild. Alternating combination chemotherapy is not more effective than either combination chemotherapy alone.