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J Periodont Res 2012; 47: 365\u2013373. \u00a9 2011 John Wiley &amp; Sons A\/S<\/jats:italic><\/jats:p><jats:p><jats:bold>Background and Objective:\u2002<\/jats:bold> Hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) is one of two volatile sulfur compounds that are known to be the main cause of oral malodor; the other is methyl mercaptan. Other known volatiles existing in mouth air do not contribute significantly to oral malodor originating in the oral cavity. Hydrogen sulfide is also known to be an etiological factor in periodontal disease. However, the effects of H<jats:sub>2<\/jats:sub>S on alveolar bone remain unclear. The objectives of this study were to determine the apoptotic effects of H<jats:sub>2<\/jats:sub>S on osteoblasts and to verify the apoptotic molecular pathways.<\/jats:p><jats:p><jats:bold>Material and Methods:\u2002<\/jats:bold> A clonal murine calvaria cell line was incubated with 50\u2003ng\/mL of H<jats:sub>2<\/jats:sub>S. To detect apoptosis, the cells were analysed by flow cytometry and ELISA. Mitochondrial membrane depolarization was assessed using flow cytometry as well. ELISA was used to evaluate the release of cytochrome\u2003<jats:italic>c<\/jats:italic> into the cytosol and to assess Fas ligand, p53, tumor necrosis factor\u2003\u03b1, interleukin IL1\u2010\u03b1 IL\u2010\u03b2, IL\u20102, IL\u20104, IL\u201010, interferon\u2010\u03b3, granulocyte\u2010colony stimulating factor and granulocyte\u2010macrophage colony stimulating factor. Caspase\u20103, \u20108 and \u20109 activities were estimated. Expression of <jats:italic>BAX<\/jats:italic> and <jats:italic>Bcl\u20102<\/jats:italic> was assessed by real\u2010time quantitative RT\u2010PCR. DNA fragmentation was detected by single\u2010cell gel electrophoresis. Fas receptors were evaluated by western blotting.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> After H<jats:sub>2<\/jats:sub>S incubation, apoptotic levels increased significantly in a time\u2010dependent manner. Mitochondrial membrane depolarization, the release of cytochrome<jats:italic>\u2003c<\/jats:italic>, p53 and caspase\u20103, \u20108 and \u20109 and DNA fragmentation were all significantly greater. <jats:italic>BAX<\/jats:italic> gene activity was upregulated, whereas <jats:italic>Bcl\u20102<\/jats:italic> remained low. Fas ligand\/Fas receptor, tumor necrosis factor\u2003\u03b1 and other cytokines were not increased to a significant degree.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> At less\u2010than\u2010pathological concentrations in gingival crevicular fluid, H<jats:sub>2<\/jats:sub>S induces apoptosis in osteoblasts. 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