Multidrug resistance (MDR) in human cancer is often associated with over-expression of the mdr-1 gene, which encodes a 170-kDa transmembrane protein, termed P-glycoprotein (P-gp). We evaluated the immunoreactivity of P-gp in oral tissues at different stages of tumorigenesis in the Indian population by flow cytometry, using the MRK-16 monoclonal antibody, which recognizes an external epitope of P-gp. The expression of P-gp was studied in human oral normal tissues (12 cases), dysplastic lesions (13 cases), primary untreated squamous-cell carcinomas (12 cases) and recurrent tumors (18 cases). Quantitative flow-cytometric analysis of P-gp expression showed a significant increase in P-gp levels in untreated primary oral tumors (p < 0.01) and in dysplastic lesions (p < 0.05) as compared with normal oral tissues. A marked significant increase in P-gp expression was observed in recurrent oral carcinomas as compared with normal oral tissues (p < 0.001) and dysplastic lesions (p < 0.01). Among recurrent tumors, a significant increase in the level of P-gp was observed in T4-stage tumors as compared with T3-stage tumors (p < 0.01). We conclude that P-gp is differentially expressed during oral tumorigenesis, and may be an indicator of the biological behavior of oral malignancies.