The goal of this project was to examine the role of endothelin-1 (ET-1) as a mediator in the pathway between air pollution exposure and the development of vascular injury. A human cohort and male mice (C57BL/6 and ecSOD-Tg) were used to evaluate changes in the ET-1 system in response to exposures of fine particulate matter (PM2.5). Human ET-1 levels were significantly associated with environmental factors and markers of vascular change, but were decreased with increased PM2.5. No association was seen between ET-1 and endothelial progenitor cells (EPCs) except for EPC-4, possibly indicating a regulatory relationship with this specific population. In mice, the expression of the ET-1 system in the cardiopulmonary tissues changed significantly with exposure, with changes varying between exposure conditions. A potentially protective effect was seen in the lungs of ecSOD-Tg animals. These data suggest that ET-1 plays an important role in the vascular response to PM2.5 exposure.