BACKGROUND The authors conducted a study to determine if salivary biomarkers specific for three aspects of periodontitis--inflammation, collagen degradation and bone turnover--correlate with clinica features of periodontal disease. METHODS The relationship between periodontal disease and the levels of interleukin-1 beta (IL-1beta), matrix metalloproteinase (MMP)-8, and osteoprotegerin (OPG) in whole saliva of 57 adults (28 "case" subjects with moderate-to-severe periodontal disease and 29 healthy control subjects) was examined in a case-control trial. RESULTS Mean levels of IL-1beta and MMP-8 in saliva were significantly higher in case subjects than in controls. Both analytes correlated with periodontal indexes, whereas, after adjustment for confounders, OPG did not. Elevated salivary levels of MMP-8 or IL-1beta (more than two standard deviations above the mean of the controls) significantly increased the risk of periodontal disease (odds ratios in the 11.3-15.4 range). Combined elevated salivary levels of MMP-8 and IL-1beta increased the risk of experiencing periodontal disease 45-fold, and elevations in all three biomarkers correlated with individual clinical parameters indicative of periodontal disease. CONCLUSIONS Salivary levels of MMP-8 and IL-1beta appear to serve as biomarkers of periodontitis. CONCLUSIONS Qualitative changes in the composition of salivary biomarkers could have significance in the diagnosis and treatment of periodontal disease.