To examine the distribution of adult T cell leukemia derived factor (ADF) in oral epithelial lesions, an immunohistochemical method using a polyclonal antibody against ADF C-terminal peptide was applied to formalin fixed and paraffin embedded tissues. All cases of periodontitis, epithelial hyperplasia, epithelial dysplasia and leukoplakia examined stained positively for ADF. Immunoreactive products were localized in the cytoplasm and/or nucleus of spinous and parakeratotic layers, but not in basal and keratinous layers. In addition, five out of nine papillomas stained positively for ADF, especially in koilocytotic cells. Eight out of 13 squamous cell carcinomas stained positively. Furthermore, ADF positive areas in oral epithelial lesions were included in the areas for protein bound SH-groups. Our results suggested that ADF may be a factor involved in the differentiation and proliferation of stratified squamous epithelium of the oral cavity.