The pathogenesis of periodontitis at the biofilm-gingival interface is modulated by a cascade of innate immune mechanisms that create a cytokine network. The dental biofilm and resultant inflammatory response have the capacity to alter the host DNA chromosomal structure through epigenetic mechanisms. The major epigenetic modification in humans is DNA methylation. These modifications have the potential to permanently alter the local gene expression by inducing tissue localized epigenetic changes that can persist within cell lineages and represent a permanently altered gene expression pattern that can affect the metabolism of the tissues and the inflammatory response. The pro-inflammatory cytokine interferon-gamma (IFN-γ) is an important regulator of the innate immune response to oral pathogens. The objective of this study was to compare the level of DNA methylation at the IFN-γ promoter between healthy and inflamed gingival tissues and correlate those findings with IFN-γ expression levels.