A combination of cisplatin, methotrexate, bleomycin, and vincristine (CABO) was assessed in advanced epidermoid head and neck cancer. Among 72 patients with recurrent or metastatic disease and measurable lesions, there were 9 complete and 27 partial responses for an overall response rate of 50%. These results were adversely affected by prior surgery plus prior radiotherapy. The median response duration was 28 weeks (16-100+) in complete responders and 16 weeks (6-84) in partial responders. CABO was also administered to 56 patients with measurable, previously untreated, locoregional disease. In these patients, complete and partial response rates were 18% and 46%, respectively. Toxic effects were generally mild to moderate. In spite of its encouraging therapeutic efficacy, CABO is unlikely to be clearly superior to single-agent chemotherapy, at least in recurrent or disseminated disease. Increased effectiveness of CABO given as initial treatment suggests that chemotherapy might play an effective adjuvant role in carefully selected patients.