BACKGROUND. The aim of the study was to investigate the effect of (1→3), (1→6)-β-glucan on the production of interleukin 10 (IL-10) and tumor necrosis factor α (TNF-α) in vitro by peripheral blood leukocytes of patients with periodontitis. MATERIAL AND METHODS. In total, 20 patients suffering from untreated severe chronic generalized periodontitis were enrolled in this study. Periodontitis was confirmed by clinical and radiologic examination. Besides, 20 periodontally healthy patients served as a control group. Peripheral venous blood was sampled from the patients, and isolated leukocytes were treated with (1→3),(1→6)-β-glucan from yeast at different concentrations. The levels of IL-10 and TNF-α secreted by the leukocytes unstimulated and stimulated with unopsonized E. coli in vitro were determined by the enzyme amplified sensitivity immunoassay method. RESULTS. Our data showed that (1→3),(1→6)-β-glucan induced a significant decrease (P<0.05) in the TNF-α level and a significant increase (P<0.001) in the IL-10 level in the media of unstimulated and stimulated leukocytes of the patients with periodontitis in comparison with those of the healthy subjects. CONCLUSIONS. The present in vitro study showed that (1→3),(1→6)-β-glucan modulated the response of leukocytes of the patients with periodontitis differently in comparison with those of the healthy subjects. It increased the release of IL-10, which is protective of the tooth-supporting tissues in patients with periodontal disease, but decreased the release of TNF-α, which is mainly responsible for the destruction of the tooth-supporting tissues during periodontal disease.