Aims: In periodontitis susceptibility individuals, disease progression involves a predominantly Th2-like immune response. Since interleukin (IL)-4 stimulates a T helper (Th)2-type of immune response and promoter polymorphisms of the interleukin-4 gene have been associated with altered IL-4 expression we assume that IL-4 promoter polymorphisms could be indicative for periodontitis. Therefore, the aim of this study was to evaluate three polymorphisms at positions -1098T/G, -590C/T and -33C/T in 121 patients with sever generalized periodontitis (attachment loss >4mm in 80% of the teeth, chronic periodontitis: n=54, mean age=49.3 ±10.0 years; aggressive periodontitis: n=67, mean age=41 ±9.9 years) in comparison to periodontitis free controls (n=81, mean age=46.9 ±10.7 years). Methods: Interleukin-4 promoter polymorphisms were analyzed by PCR-SSP (CTS-Kit, Heidelberg). Distributions of single alleles, genotypes, and haplotypes were calculated by Chi2-Test with Yates correction or Fisher's exact test. Risk factor analyses were carried out by logistic regression under consideration of established cofactors for periodontitis such as age, gender, smoking status, and plaque index. Results: The mutant allele IL-4 -1098 G and the haplotype -1098, -590, -33 GCC increased the adjusted Odds ratio for both, chronic periodontitis (OR=4.1-5.3) and aggressive periodontitis (OR=3.8-5.0). Genotypes and haplotypes with the mutant allele T at the positions -590 and/or -33 were positive associated only with an aggressive periodontitis (OR=2.3-3). Conclusions: Genotypes and haplotypes with the mutant allele G at position -1098 were indicative for both, CP and AP. Polymorphisms (C>T) at positions -590 and -33 (high interleukin-4 producer genotypes) increased the Odds ratio for an AP. Therefore it would be interesting to assess a putative association of IL-4 gene polymorphisms to IL-4 production in a further study. Keywords: chronic periodontitis, aggressive periodontitis, interleukin-4, promoter polymorphisms