Indoor allergens such as house dust mite (HDM) are a contributing factor to the development of allergy and asthma in children. There is increasing evidence that air pollutants such as ozone may affect the initiation or severity of atopic diseases. We have previously established that experimental exposure of adult rhesus monkeys to HDM produces a clinical and pathologic syndrome similar to that of human asthmatics. In order to understand the combined effects of ozone and HDM aeroallergens during a period of pulmonary and immune system development, we exposed infant rhesus monkeys for 22 weeks to one of four regimens: (1) filtered air, (2) priming doses of HDM plus adjuvant parenterally followed by biweekly aerosolized HDM, (3) ozone at 0.5 ppm for 8 h/d 5 days on and 9 days off, or (4) HDM plus ozone. In response to HDM exposure, epithelial and mesenchymal components of the airway wall were altered in association with elevated baseline airway obstruction. Exposure to ozone exacerbated the remodeling changes associated with HDM exposure. Similarly, peripheral blood and lavage T-helper cell activation was enhanced in response to HDM and ozone exposures. Within specific airway generations, the abundance of activated T lymphocytes, dendritic cells, and eosinophils were also affected by HDM and ozone exposure regimens. Our cumulative findings indicate that air pollutants have a modulatory effect on the pulmonary and systemic response to allergens.