Background: Exposure to high levels of allergens in sensitized asthmatic patients causes worsening of pulmonary function in experimental studies. Chronic exposure to lower, naturally occurring levels of allergens might increase the severity of asthma. Objective: We sought to study the associations between sensitization and exposure to common indoor allergens (dust mite, cat, and dog) in the home on pulmonary function, exhaled nitric oxide (eNO), and airway reactivity in asthmatic patients. Methods: Dust samples were collected from the living room carpet and mattress of 311 subject's homes, and Der p 1, Fel d 1, and Can f 1 concentrations were measured by using ELISAs. Spirometry, nonspecific bronchial reactivity, and eNO were measured. Results: Subjects both sensitized and exposed to high levels of sensitizing allergen had significantly lower FEV1 percent predicted values (mean, 83.7% vs 89.3%; mean difference, 5.6%; 95% CI, 0.6%-10.6%; P = .03), higher eNO values (geometric mean [GM], 12.8 vs 8.7 ppb; GM ratio, 0.7; 95% CI, 0.5-0.8; P = .001), and more severe airways reactivity (PD20 GM, 0.25 vs 0.73 mg; GM ratio, 2.9; 95% CI, 1.6-5.0; P <.001) compared with subjects not sensitized and exposed. No significant effect of the interaction between sensitization and exposure was found for FEV1 percent predicted and eNO values. However, there was a significant effect of the interaction between sensitization and exposure to any allergen (P = .05) and between sensitization and exposure to cat allergen (P = .04) for nonspecific bronchial reactivity. Conclusion: Asthmatic subjects who are exposed in their homes to allergens to which they are sensitized have a more severe form of the disease.