Several studies have investigated the genetic polymorphisms for cytokines as potential genetic markers for periodontitis. The aim of this study was to determine the prevalence of IL1 cluster genes polymorphisms and their association with chronic periodontitis in the Macedonian population. The group of 114 unrelated Macedonian subjects with chronic periodontitis and 301 periodontitis-free Macedonian subjects were studied. DNA was isolated from peripheral blood leukocytes by phenol-chloroform extraction method. Cytokine genotyping was performed by PCR-SSP. The population genetics analysis package (PyPop) was used for analysis of the cytokine data for this report. Crude odds ratio (OR) was calculated as estimates of the relative risk with 95 % confidence interval (CI). Genotype frequency of IL1B -511/C:T was significantly higher in patients with periodontitis than in controls (OR=2.11, 95 % CI=1.35-3.32, p=0.001). IL1 cluster gene haplotype frequencies of TTTCT and TCTTT were associated with higher risk for periodontitis (OR=5.06, 95 % CI=1.68-15.26, p<0.0014 and OR=8.35, 95 % CI=1.67-41.69, p<0.002, respectively). No significant association of IL1 composite genotype (IL1 -889A:IL1B +3962) with periodontitis in Macedonians was found. The latter association was found to be significant in genotype IL1B -511/C:T, haplotype TTTCT, and haplotype TCTTT, but without significant association in IL1 composite genotype (Tab. 5, Ref. 43).