It is well establishedthat Porphyromonas gingivalisis one of the major pathogens of adult periodontitis. P. gingivalis produces an outer membrane protein with a molecular mass of 40-kDa (40k-OMP). In the present study, in order to assess the potential for application of 40k-OMP in the development of an antiperiodontal disease vaccine, we analyzed 40k-OMP-specific CD4+ T helper (Th) cell responses induced in the mucosal as well as systemic compartments when 40k-OMP was administered nasally. When CD4+T cells that were isolated from cervical lymph nodes (CLN) and spleens of mice immunized with 40k-OMP plus cholera toxin (CT) as adjuvant were re-stimulated with 40k-OMP in vitro, significant levels of proliferative responses were induced. In contrast, essentially no increased proliferation occurred in CLN and spleens taken from mice given 40k-OMP alone. Analysis of T helper (Th) 1 (IFN-y) and Th2 (IL-4, IL-5 and IL-6) cytokine responses showed that 40k-OMP-specific Th cells from both CLN and the spleen produced significant levels of IL-4, IL-5 and IL-6 but did not result in changes in IFN-y production. In contrast, marginal levels of IL-4, IL-5 and IL-6 production were seen in mice given 40k-OMP alone nasally. These results suggest that nasal administration of 40k-OMP plus CT as an adjuvant can elicit 40k-OMP-specific Th2-type cytokine responses in both mucosal and systemic compartments. Further, the nasal 40k-OMP vaccine possesses the potential for antiperiodontal vaccine.