Thirty evaluable patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck region previously treated with cisplatin-based chemotherapy were treated with a combination of methotrexate, vinblastine, epidoxorubicin, and bleomycin as second-line chemotherapy. Besides surgery and/or radiotherapy all patients had previously received chemotherapy as induction therapy or as palliation for recurrent disease. Only 20% of patients achieved a partial objective response with a mean duration of 5.6 months (range 3.2-6.2), and 30% of patients had a stabilization of disease with a mean duration of 4.2+ months (range 3.8-6.0). Patients who responded had rhinopharyngeal carcinoma, poorly differentiated histology, or they had not been previously treated with radiotherapy. All remaining patients (50%) progressed. Toxicity was significant with grade 3-4 leukopenia in 30% of cases, grade 2-3 mucositis in 40% of patients, and grade 2-3 vomiting in 43% of cases. In consideration of the dismal clinical results and of the significant toxicity recorded, we do not recommend to use this combination as second-line therapy in recurrent head and neck cancer. Further chemotherapy should be reserved to carefully selected cases with a reasonably high chance of response.