Although research on the influence of neighborhoods on the development of youth is growing, few researchers have examined the impact of neighborhood quality on physiological outcomes or across gender. The present experiment examined gender differences in the association of neighborhood quality and cardiovascular reactivity (increased blood pressure, BP, in response to stress) among 77 healthy African American adolescents (46% male; M age = 14 years). Participants took part in a cold-face stimulus task to determine reactivity scores. After controlling for baseline BP, family income, and parental education, poorer neighborhood quality was associated with increases in both systolic and diastolic BP to the cold-face task for females, and decreases in BP for males. Adolescents’ reports of life stress and support from family members did not explain the differential effect of neighborhood quality across gender. Implications for future research are discussed.