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Introduction: Polymorphisms within innate immunity genes are associated with allergic phenotypes but results are variable. These associations were not ana lyzed with respect to allergen exposure. We investigated associations of TLR and CD14 polymorphisms with allergy phenotypes in the context of house dust mite (HDM) exposure. Material and methods: Children, aged 12-16 years ( n = 326), were recruited from downtown and rural locations and assessed by allergist. Skin prick tests, total and HDM-specific sIgE measurements were done. HDM allergen concentrations in dust were measured. Genetic polymorphisms were identified using restric tion fragment length polymorphism (RFLP). Results: Allergic rhinitis, asthma and atopy were more prevalent in urban area. Although HDM allergen concentrations were higher in rural households, sIgE were present more frequently in urban children. In the whole population no association was found between HDM exposure and sensitization. In children with CD14/–159CC, CD14/–159TT and TLR9/2848GA genotypes increased expo sure to HDM was associated with reduced incidence of allergic rhinitis. Signif icant associations of increased HDM exposure with reduced incidence of atopy were found for the whole population and subjects with CD14/–159CC, CD14/–1359GT, TLR4/896AA and TLR9/2848GA genotypes. Among children with CD14/–159CC and CD14/–1359GG significant positive correlation between HDM allergen concentrations in household and sensitization to HDM was observed. In contrast, protective effect of high HDM allergen exposure against specific sensitization was seen in subjects with TLR4/896 AG. Conclusions: Development of specific sensitization and allergy may be associ ated with innate immune response genes polymorphisms and is modified by allergen exposure.