<p>Researchers are paying increasing attention to the environmental aspects of the neighborhood in which children and adolescents are raised and their role in psychobiological development. Factors that are distal to the home environment, such as green spaces and pollution levels, have been shown to be associated with mental health in youth, even when accounting for variance explained by more proximal home factors (e.g., family socioeconomic status). Researchers have posited that individuals vary in their susceptibility to adverse conditions, which can be operationalized as psychobiological reactivity; this formulation, however, has not been tested with respect to air quality. Here, we assessed internalizing and externalizing symptoms in 133 adolescents at four time points, each approximately two years apart, beginning in early puberty. Psychobiological reactivity was assessed during the Trier Social Stress Test. We found that adolescents living in neighborhoods with poorer air quality, measured by particulate matter, ozone levels, and days with temperatures over 90°F, had higher levels of internalizing and externalizing symptoms if they were also less psychobiologically reactive. These findings support the formulation that levels of psychobiological reactivity index susceptibility to the environment and highlight the importance of reducing air pollution to help promote optimal adolescent health.</p>