Clinical and pathological observation has been carried out in 68 cases of oral leukoplakia examined in our department and results are as follows.1) The patients consisted of 42 males and 26 females, and a high prevalence was observed in males in their forties.2) Foci most frequently occured on the gingiva, then on the tongue, lips and buccal mucous membrane, and were found least frequently on the oral floor.On the gingiva, a great many white-spotted types and plateau types occurred but on the tongue erosive types were seen most frequently.On the lips and buccal mucous membrance, many white-spotted types were observed but on the oral floor only one white-spotted type and one erosive type were seen. Five cases were accompanied by cancer and four cases became malignant, all of these being derived from the erosive type.3) In relation to smoking, the incidence was 70% in males and 44% in females and was higher than the average percentage of adult smokers in our country. Score of Brinkman index (B.I.) was 562 on average and this was higher then B.I. 400 which is a standard value of the high-risk group for lung cancer, therefore smoking is considered to be the cause of this disease.4) Investigation of the relationship between metal restorations and dentures using patch testing revealed in 53% of a positive reaction cases. Many positive reactions were observed toward metals most commonly used in dental materials, and this suggested a great possibility of local stimululation by metal allergy. Cases associated with a local stimulus deriving from unfitted dentures, dental caries and metal allergies amounted to 56%.5) In the results of glucose tolerance testing, a significant difference was not shown in comparison with healthy persons in the same age bracket. Levels of serum immunoglobulins IgA, IgG, IgM, and vitamin A, vitamin B2 and cholesterol in blood were within normal values.The above results indicate that systemic factors were not influencing factors as much as were local factors.6) In histological studies, as to the first pattern (that without a differential pattern in epithelial cells, with a thin epithelial layer a great difference was not observed in comparison with other groups. However, as to the second pattern (that without a differential pattern in the epithelial cells, with a thickened epithelial layer) the epithelial layer was thickened and intercellular edema in the squamous cell layer and prolongation and acumination of the rete ridge were shown. As to the third pattern (one accompanied by a differential pattern in the epithelial cells) the tissues observed were similar to those in the second pattern, but cells with enlarged nuclei and increased chromatin content in the basement layer, and on increased mitosis rate were observed.In electron microscopic examination, in the basement cell layer, Langerhans cells (L.C.) were often observed.7) In the chemical examination of immunohistologic patterns clinically found, the degree of infiltration of sub-epithelial tissue, and S-100 protein-positive cells in the epithelium were analysed.Results showed that the number of S-100 protein-positive cells in the epithelia were increasing significantly in plateaupatterns, accompanied by erosion and cancer patterns.Pathologically, the relationship between degree of infiltration of sub-epithelial tissue and S-100 protein-positive cells was clearly observed to be correlative.The increase in L.C. in the case of plateaupattern and erosivepattern leukoplakia and in cases where lesions developed into cancer is considered to suggest functional acceleration of antigen recognition mechanism in the foci, together with the acceleration of cellular infiltration to sub-epithelial tissue in these patterns.