Background: Neopterin is a member of the pteridine family, It is produced by human monocytes/macrophages and dendritic cells from guanosine triphosphate (GTP) upon stimulation with

interferon gamma (IFNγ). It has been known to be a biological marker associated with cell-mediated immunity. Objectives: The aim of this study is to measure the levels of neopterin in saliva and serum in periodontitis patients comparing them with periodontally healthy subjects. Method: Saliva and serum samples were collected from 23 systemically healthy periodontitis patients and 23 periodontally healthy control individuals. Clinical periodontal parameters (plaque index (PI), probing pocket depth (PPD), gingival recession (GR), clinical attachment loss (CAL), and bleeding on probing (BOP)) and saliva flow rates were recorded. Salivary and serum neopterin and 7-dihydroneopterin (7NP) levels were evaluated with Tandem Mass Spectrometry (LC-MS/MS) method. Results: The concentrations of free and total salivary neopterin were statistically significantly higher in the patients with periodontitis compared with control group (p<0.001). In periodontitis group 7NP saliva was also significantly higher than control (p<0.001). There was no significant difference in serum between periodontitis and control groups. 7NP levels in the saliva were significantly and positively correlated with all the clinical periodontal parameters (PI, PPD, BOP, and CAL; p<0.01) Conclusion: Our results demonstrated that salivary concentrations of neopterin (free, total and 7NP) were associated with periodontitis. This study suggests that salivary neopterin concentrations may reflect local immune activation even in situations where no systemic activation can be detected.