BACKGROUND A growing body of evidence suggested that interleukin (IL)-21 enhances the effector phase during T-cell responses. The aim of our study is to determine the levels of IL-21 in periodontal sites from patients with chronic periodontitis and controls. METHODS The population studied consisted of 34 patients (15 with chronic periodontitis and 19 healthy patients). Twenty samples (10 gingival crevicular fluid [GCF] and 10 gingival biopsies) were collected from each group before the patients with periodontitis received periodontal treatment. Total protein concentrations were measured in all samples; the presence of IL-21 was confirmed by immunohistochemistry and Western blot, and IL-21 levels were quantified through an enzyme-linked immunosorbent assay. Statistical analyses were performed using statistical software. Data were expressed as patient means ± SDs or medians (interquartile ranges) by using the χ(2), Student t, and Mann-Whitney U tests. RESULTS GCF IL-21 was mainly detected in patients with chronic periodontitis (P <0.05). Levels of IL-21 in gingival tissues were significantly higher in patients with chronic periodontitis compared to healthy individuals (P <0.05). The Western blot and immunohistochemical staining confirmed the presence of IL-21 in periodontal tissues and GCF. CONCLUSION IL-21 was highly expressed in patients with chronic periodontitis, especially in gingival biopsies; therefore, IL-21 might play a role in the T-cell response.