Respiratory allergic diseases and symptoms are extremely prevalent in the industrialized world. Allergic sensitization is characterized by elevated levels of immunoglobulin (Ig) E and is a risk factor for the development of asthma and allergic disease. The 2005-2006 Nutrition Examination and Health Survey (NHANES) is a US population-based survey that included the largest sample of IgE antibody samples in US history and an expanded questionnaire section on respiratory allergies. Air pollution has been investigated as a possible risk factor for both allergic sensitization and respiratory allergic disease. Despite extensive investigation, the relationship between ambient air pollution, allergic sensitization, and respiratory allergic diseases remains unclear. To better understand the relationship between ambient air pollution, allergic sensitization, and respiratory allergic diseases, we linked monitored annual average concentrations of nitrogen dioxide (NO2), particulate matter ≤ 10 µm (PM10), particulate matter ≤ 2.5 (PM2.5), and summer concentrations of ozone (O3) from the US Environmental Protection Agency Air Quality System, to participants ages 6 and older in the 2005-2006 National Health and Nutrition Examination Survey (NHANES). In addition to monitor-based air pollution estimates, we used air pollution estimates from the Community Multiscale Air Quality model to increase the number of rural participants in our sample. We used logistic regression with population-based sampling weights to calculate adjusted prevalence odds ratios (aOR) per 10 ppb increase for O3 and NO2, per 10 µg/m3 for PM10, and per 5 µg/m3 for PM2.5 adjusting for race, gender, age, socioeconomic status, smoking, body mass index and urban/rural status. Results: Using CMAQ data, increased levels of NO2 were associated with positive IgE to any (aOR 1.15, 95% CI 1.04, 1.27), inhalant (aOR 1.17, 95% CI 1.02, 1.33) and outdoor (aOR 1.16, 95% CI 1.03, 1.31) allergens. Increased levels of PM2.5 were associated with indoor allergen-specific IgE (aOR 1.24, 95% CI 1.13, 1.36). We found positive associations between current allergies and increased O3 levels (per 10 ppb) using modeled data [aOR=1.25 (1.10, 1.43)] and monitored data [aOR=1.17 (0.98, 1.40)]. We found a negative association between PM10 and hay fever using monitored data (aOR =0.67 (0.47, 0.97). Although the associations were consistent across the data, the association between current allergies and monitored O3 lost significance after adjustment for confounders. Results with monitored data and CMAQ data were similar for non stratified analyses. Conclusion: These findings suggest that ambient air pollution is associated with allergic sensitization. The finding of an association with NO2 and allergic sensitization is seen for both monitored and modeled data and across several categories of allergen-specific IgE. To our knowledge, our study is the first to assess the relationship between air pollution and allergic sensitization in a nationally representative sample of the US population. In addition, we found consistent associations between O3 and current allergies overall. We did not find consistent evidence for associations of NO2, PM2.5, PM10 with asthma or the other allergic outcomes.