Modified Project Summary/Abstract Section Posttraumatic distress disproportionately affects Hispanic immigrants due to high rates of trauma exposure in their home countries and continued trauma. The proposed study will collect longitudinal data from 400 Hispanic immigrant adults to examine how trauma exposure at various stages— prior to, during migration, and while settling in the U.S.— concurrently and prospectively influences risk for posttraumatic distress and quality of life via the biological pathway of inflammation. In collaboration with established community partners, participants will be recruited. Follow-up data collected one year later will assess trauma exposure while settling in the U.S., posttraumatic distress, and quality of life. Using the inflammatory hypothesis of persistent posttraumatic distress (Gill et al., 2009) as a conceptual framework, the proposed study incorporates state-of-the-art biological markers and mixed methods to provide novel information about mechanisms that underlie health risk and foster resilience across domains and levels. Specific Aim 1 is to concurrently and prospectively evaluate the effect of trauma exposure prior to and during migration on immigrants’ posttraumatic distress and quality of life. Specific Aim 2 is to concurrently and prospectively evaluate the effect of trauma exposure prior to and during migration on immigrants’ biological (immune) function, testing inflammation as a mechanism of health disparity. Specific Aim 3 is to identify factors within the sociocultural and personal environment domains (at individual/interpersonal levels) that moderate links identified in Aim 2. Specific Aim 4 is to assess how (post-migration) trauma exposure while settling in the U.S. prospectively affects posttraumatic stress and quality of life. Knowledge gained will (1) propel scientific evidence regarding how multi-domain, multi-level contextual factors influence the health of vulnerable populations with the goal of reducing existing disparities; and (2) inform the development of culture and context sensitive interventions. This is the first prospective, longitudinal study to use a multi-domain, multi-level approach including biology to identify mechanisms of health risk and resilience among Hispanic immigrants. We innovate by assessing how trauma exposure at various stages— prior to, during migration, and while settling in the U.S.— relates to disparities in health outcomes. Further, we probe new sources of potential trauma for migrants. By innovatively studying resilience at the biological level in this population, this study takes the first steps towards the development of novel therapeutics to address disparities in posttraumatic distress and quality of life.