Interleukin-10 regulates pro-inflammatory cytokines, including those implicated in alveolar bone resorption. We hypothesized that lack of interleukin-10 leads to increased alveolar bone resorption. Male interleukin-10(-/-) mice, on 129/SvEv and C57BL/6J background, were compared with age-, sex-, and strain-matched interleukin-10(+/+) controls for alveolar bone loss. Immunoblotting was used for analysis of serum reactivity against bacteria associated with colitis and periodontitis. Interleukin-10(-/-) mice had significantly greater alveolar bone loss than interleukin-10(+/+) mice (p = 0.006). The 30-40% greater alveolar bone loss in interleukin-10(-/-) mice was evident in both strains, with C57BL/6J interleukin-10(-/-) mice exhibiting the most bone loss. Immunoblotting revealed distinct interleukin-10(-/-) serum reactivity against Bacteroides vulgatus, B. fragilis, Prevotella intermedia, and, to a lesser extent, against B. forsythus. The results of the present study suggest that lack of interleukin-10 leads to accelerated alveolar bone loss.