A study was carried out to investigate whether smoking had any effect on the Langerhans cells in the oral mucosa, which might throw light onto the mechanism of malignant transformation of some keratotic lesions in the oral cavity. Thirty-two cases of keratotic lesions from biopsy specimens of smokers and non-smokers were studied. Langerhans cells were identified by immuno cytochemical staining for 5100 proteins and their densities quantified. Smokers were associated with a significant reduction in the Langerhans cell population compared to non-smokers. The mean values of Langellans cell density in light smokers and heavy smokers were 2 2 2 28.64/mm and 33.421mm respectively compared to 66.51/mm in non- smokers. There was a dose-response relation between the number of cigarettes smoked daily and the effect on cell counts. These findings of a local immunological effect of smoking on oral epithelium may explain the means by which cigarette smoking contributes to the development of oral cancer.