Exposure to high levels of fine particle air pollution (PM2.5) is associated with adolescent pathophysiology. It is unclear, however, if PM2.5 is associated with physiology within psychosocial contexts, such as social stress, and whether some adolescents are particularly vulnerable to PM2.5-related adverse effects. This study examined the association between PM2.5 and autonomic reactivity to social stress in adolescents and tested whether symptoms of anxiety and depression moderated this association.Adolescents from Northern California (N = 144) participated in a modified Trier Social Stress Test while providing high-frequency heart rate variability and skin conductance level data. PM2.5 data were recorded from CalEnviroScreen. Adolescents reported on their own symptoms of anxiety and depression using the Youth Self-Report, which has been used in prior studies and has good psychometric properties (Cronbach's α in this sample was .86).Adolescents residing in neighborhoods characterized by higher concentrations of PM2.5 demonstrated greater autonomic reactivity (i.e., indexed by lower heart rate variability and higher skin conductance level) (β = .27; b = .44, p = .001, 95% CI = 0.19 to 0.68) in response to social stress; this association was not accounted for by socioeconomic factors. In addition, adolescents who reported more severe anxiety and depression symptoms showed the strongest association between PM2.5 and autonomic reactivity to social stress (β = .53; b = .86, p < .001, 95% CI = 0.48 to 1.23).Exposure to PM2.5 may heighten adolescent physiological reactivity to social stressors. Moreover, adolescents who experience anxiety and depression may be particularly vulnerable to the adverse effects of PM2.5 on stress reactivity.