CD14 and toll-like receptor 4 (TLR4) are involved in host's immune response to bacterial pathogens including periodontal bacteria. Functional important gene polymorphisms are described for both genes. The aim of this study was to evaluate links between genetic polymorphisms of CD14 and TLR4 and risk markers of periodontitis in a multivariate model. One hundred and thirty-three periodontitis patients (chronic: n = 60, aggressive: n = 73) and 80 healthy controls without periodontitis were included in the study. Polymorphisms in CD14 c.-159C>T and in TLR4 Asp299Gly, Thr399Ile were determined by restriction fragment length polymorphism analyses. The clinical investigation included smoking status, plaque and bleeding indexes, pocket depth and attachment loss. Subgingival bacterial colonization was analysed molecularbiologically using the micro-Ident test. Prevotella intermedia occurred less frequently in individuals positive for the TT genotype of CD14 in bivariate analysis (odds ratio = 0.36%, confidence interval: 0.14-0.91, P = 0.045). In binary logistic regression analyses, the occurrence of this bacterium was significantly decreased in TT carriers (odds ratio = 0.31%, confidence interval: 0.81-0.12, P = 0.017) considering age, smoking and maximum clinical attachment loss at microbial test site as confounding factors. However, no significant association with chronic and or aggressive periodontitis and polymorphisms in CD14 and TLR4 could be proven. Although the CD14 c.-159C>T polymorphism could be shown to be associated with subgingival colonization with P. intermedia, there is no evidence that CD14 and TLR4 polymorphisms investigated are independent risk factors for chronic or aggressive periodontitis in German periodontitis patients.