The significant increase in oral cancer mortality necessitates further research on the mechanisms of tumorigenesis. It was the aim of this study to compare the permeability, lipid composition and histopathological characteristics of oral leukoplakia with non-lesional specimens of the same region in 30 cases as well as 11 specimens originating from healthy control buccal mucosa. The permeability (Kp) of tissue biopsies to tritiated nitrosonornicotine was determined in a continuous through-flow perfusion system, lipids were extracted and identified by thin-layer chromatography, and thickness of epithelium and keratin layer assessed by histopathological methods. Results of the measurements showed that the permeability to the tobacco carcinogen, nitrosonornicotine for leukoplakic tissue was higher than for normal control buccal specimens. Non-lesional areas of buccal mucosa, adjacent to leukoplakias, showed hyperplasia and significantly higher permeability values than both leukoplakic and normal buccal control mucosa. The lipid content of the non-lesional sites was intermediate between the increased values of the leukoplakic lesion and of normal control mucosa. The data strongly suggest that the presence of tobacco in the oral cavity may bring about generalized changes even in regions that do not show leukoplakia.