Objective The purpose of this studywas to investigate the relationship between apoptosis and proliferation of oral mucosa in lesions of leukoplakia and the role of apoptosis in the pathogenesis of this common oral disease.Methods The mucosa was obtained from the leukoplakia lesions from 6 patients, with average age of 57 years, and all the patients had not received any treatment before this investigation. The lesionswere located on the lip (1), gingiva (1), tongue (2) and buccal mucosa (2). All the patients did not have any systemic diseases. Otherthree normal oral mucosa tissueswere collected as the control. In situ terminal de- oxynucleotidyl transferase end-labeling (TUNEL) and avidin-biotin peroxidase complex (ABC) immunohistochemical assaywere used to detect single-strand DNA breaks and proliferating cell nuclear antigens (PCNA). The negative control slides were treated with the tris saline bufferto substitute the terminal deoxynucleotidyl transferase (TdT) and PCNA-Ab in the assay. Five consecutive high pow- er fieldswith the magnification of 400 were used to search for positive stained keratinocytes.Results Comparedwith the normal mu- cosa, the keratinocytes in leukoplakia showed positive apoptotic signals in the nucleus of suprabasal epithelial layers, while PCNA- positive stain was present in the basal position. In the connective tissue, positive apoptotic signalswere found in lymphocytes and the endothelia of blood vessels.Conclusion The results indicate that the death of cells in leukoplakia is partly due to apoptosis which may play an important role in the genesis of oral leukoplakia.