One established mechanism of multidrug resistance is elevated expression of P-glycoprotein. The expression of P-glycoprotein by immunohistochemistry was examined in squamous cell carcinomas of the head and neck using a newly developed monoclonal antibody, UIC2, which is specific to the human MDR1 gene product and recognizes an external epitope of the protein. P-glycoprotein was detected in 60% of the samples. MDR1 expression was compared with clinical response to chemotherapy in eight patients who received MDR1-dependent drugs and response was accurately predicted in seven (89%) of eight patients. Positive P-glycoprotein staining correlated with the degree of tumor differentiation, but not with other clinical factors. Therefore, analyzing the expression of P-glycoprotein may play a role when planning chemotherapeutic regimens for patients with head and neck cancer and may be an additional prognostic and diagnostic tool in these patients.