Host genetic predispositions to dysregulated immune response can influence the development of the aggressive form of periodontitis (AgP) through susceptibility to oral dysbiosis and subsequent host-microbe interaction. This case-control study aimed to perform a multilocus analysis of functional variants in selected interleukin (IL) genes in patients with the generalized form of AgP in a homogenous population. Twelve polymorphisms inIL-1gene cluster,IL-6and its receptor,IL-10,IL-17A, andIL-18were determined in 91 AgP patients and 210 controls. Analysis of seven selected periodontal bacteria in subgingival sulci/pockets was performed with a commercial DNA-microarray kit in a subgroup of 76 individuals. The pilot in vitro study included stimulation of peripheral blood monocytes (PBMC) from 20 individuals with periodontal bacteria and measurement of IL-10 levels using the Luminex method. Only the unctional polymorphismIL-10-1087 A/G (rs1800896) and specificIL-10haplotypes were associated with the development of the disease (p< 0.05,P-corr> 0.05). Four bacterial species occurred more frequently in AgP than in controls (p< 0.01,P-corr< 0.05). Elevated IL-10 levels were found in AgP patients, carriers ofIL-10-1087GG genotype, and PBMCs stimulated by periodontal bacteria (p< 0.05,P-corr> 0.05). We therefore conclude that a combination of genetic predisposition to the altered expression ofIL-10and the presence of specific periodontal bacteria may contribute to Th1/Th2 balance disruption and AgP development.