Although periodontitis is a chronic inflammatory disease caused by a group of so-called periodontopathic bacteria, autoimmune mechanisms have also been implicated in the disease process. Recently, a unique subset of lymphocytes designated natural killer (NK) T cells expressing the Valpha24JalphaQ invariant T cell receptor (TCR) has been reported to have a regulatory role in certain autoimmune diseases. Therefore, we investigated the proportion of the invariant Valpha24JalphaQ TCR within the Valpha24 T cell population in periodontitis lesions and gingivitis lesions using single-strand conformation polymorphism methodology. NK T cells were identified with a specific JalphaQ probe whereas the total Valpha24 TCR was identified using an internal Calpha probe. NK T cells were a significant proportion of the total Valpha24 population both in periodontitis lesions and to a lesser extent in gingivitis lesions but not in the peripheral blood of either periodontitis patients or nondiseased controls. Using immunohistochemistry, some of Valpha24(+) cells in the periodontitis lesions seemed to associate with CD1d(+) cells, which are specific antigen-presenting cells for NK T cells. Although the mechanism underlying the elevation of NK T cells in periodontitis and in gingivitis lesions remains unclear, it can be postulated that NK T cells are recruited to a play regulatory role in the immune response to bacterial infection.