42 consecutive patients with head and neck squamous cell carcinoma were entered into a multi-agent chemotherapy protocol including: bleomycin and Cis-platinum (in continuous infusion), sequenced with methotrexate and Vinblastine (by bolus infusion). Hydroxyurea was substituted for bleomycin when the accumulative dose of bleomycin reached 400 units. 9 of 11 patients with untreated disease responded to chemotherapy, with 36.4% showing complete response following the second cycle. After completion of all therapy, complete response had occurred in 10 patients and partial response in 1. At a median follow-up of 1 year, 9 patients are disease-free, and the median duration of response has not yet been reached. For recurrent disease, the overall regression rate is 45.1% (14/31). The median duration of response is 6.5 months, with responding patients showing a median survival of 8.7 months and non-responders, 5.4 months. The data for response and survival are comparable to previous studies and suggest that toxic manifestations may be mitigated by careful attention to nutrition and production of an anabolic state prior to therapy.