Although there is clear evidence that individual racism experiences can have negative effects on mental health, few studies have examined structural racism and discrimination (SRD) as a determinant of mental health, nor have studies examined the mechanisms by which structural racism undermines mental health. This project will elucidate: (i) neurophysiological stress mechanisms by which SRD impacts mental health; and (ii) sociocultural factors that influence the impact of SRD on mental health during the transition to adulthood. The central hypothesis is that SRD will predict poor mental health by impacting neurophysiological stress systems, while individual, family, and sociocultural factors will moderate the impact of structural racism on neurophysiology and mental health. This hypothesis will be tested across three specific aims: 1) Determine the associations between organizational/institutional, neighborhood/community, and societal indicators of SRD (e.g., residential segregation, discriminatory lending practices, school disciplinary and criminal justice practices, proximity to racist statues) and mental health by measuring aspects of SRD at the level of state, neighborhood, and census tract; 2) Elucidate neurophysiological stress mechanisms linking SRD and mental health at three levels: corticolimbic, autonomic, and immune; and 3) Identify individual vulnerability (i.e., chronic exposure to poverty and violence) and family, cultural, and community resilience factors (e.g., racial identity, racial socialization, religious involvement) that moderate the SRD-mental health link. We will test these associations in a sample of 850 young adults from the Fragile Families and Child Wellbeing Study. This ongoing study of children born to families from predominantly low-income backgrounds has multiple scientific strengths: 1) Children were assessed at birth, 1, 3, 5, 9, 15, 21, and 22 years; 2) The sample is representative of children born in large cities with considerable variation across cities in segregation and criminal justice policy and implementation; and 3) Participants are entering early adulthood, a critical developmental period of increased risk for poor mental health outcomes. By identifying these SRD-mental health pathways using multi- level (i.e., individual, institutional, and cultural racism) and multi-domain (i.e., organization/institutional, neighborhood/community, societal) indicators of racism across diverse geographic units, with multiple measures of neurophysiology, and measurement of sociocultural resilience factors in a 22-year longitudinal birth cohort sample, the study will provide a strong evidence-base to inform new opportunities for structural and therapeutic interventions to decrease structural racism, eliminate racial health disparities, and promote health equity.