Background and objectives: IL-17 is a novel T cell-derived cytokine that promotes inflammatory responses. It is presence in inflamed gingival tissues and gingival crevicular fluid of periodontitis patients. In this study we investigated the effects of IL-17 alone or in combination with IFN-Y on the immune modulation of human gingival fibroblasts (HGFs) which would contribute to pathogenesis of periodontium. Methods and results: Various concentrations of IL-17, IFN-Y or the combination of these two cytokines were added to HGF cultures. The expression of ICAM-1, HLA-DR, and CD40 was assessed by flow cytometry and IL-8 production was determined by ELISA. Our results demonstrated that IFN-Y markedly induced expression of HLA-DR and ICAM-1 and slightly induced CD40 expression on HGFs. In contrast, IL-17 had no effect on these molecules. When combined, IL-17 did not enhance IFN-Y-induced HLA-DR and CD40 expression but significantly up-regulated ICAM-1 expression (p<0.01), Unlike IFN-Y, IL-17 induced IL-8 production from HGFs. When combined, IFN-Y synergistically enhanced IL-17-induce IL-8 production in all HGF lines (p<0.05). Conclusions: These findings indicate that IL-17 and IFN-Y have different effects on HGFs regarding the expression of co-stimulatory molecule and adhesion molecule as well as immune mediator. All of these molecules are critical in controlling immune response, thus indicating the immunoregulatory role of locally produced IL-17 and IFN-Y in inflamed periodontal tissue.