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Phthalates have been associated with respiratory symptoms in adults; they may enhance effects of inflammatory compounds. To assess the potential interactions of phthalates and endotoxin on respiratory and allergic symptoms in adults, we used cross-sectional information from the 1091 adults with complete data on urinary phthalates and house dust endotoxin from NHANES 2005–2006. We used multivariable logistic regression to assess whether endotoxin levels modified the association between nine phthalate metabolites and four current allergic symptoms (asthma, wheeze, hay fever, and rhinitis). Endotoxin was classified into tertiles (<10, 10–25, >25 EU/mg dust). Urinary phthalate and dust endotoxin levels were not correlated (r < |0.02|). Under low endotoxin conditions, no associations between phthalates and respiratory outcomes were observed. Under medium or high endotoxin conditions, exposure-response relationships were observed between specific phthalates and wheeze and asthma. For wheeze, three phthalates (mono-benzyl phthalate (MBzP), mono(carboxyoctyl) phthalate (MCOP), and di-ethylhexyl phthalate (DEHP) had significant interactions with endotoxin); for asthma, two phthalates (MCOP and mono(carboxyoctyl) phthalate (MCNP)) had significant interactions. Endotoxin did not modify the associations between phthalates and hay fever or rhinitis. These results are consistent with the hypothesis that endotoxin enhances the respiratory toxicity of phthalates; however this cross-sectional study cannot address key temporal issues. The lack of an association between wheeze or asthma and phthalates when endotoxin exposure was low suggests that phthalates alone may not increase these symptoms.Phthalates are associated with allergy and asthma, but the potential mechanisms are unclear.Individuals living in homes with low endotoxin showed no association between phthalates and respiratory outcomes.An interaction was present for phthalates and endotoxin for respiratory symptoms of wheeze and asthma, but not rhinitis and hay fever.