Abstract Since blacks have long had a much lower life expectancy than whites, we argue that a dramatic and overlooked element of racial disadvantage and adversity is exposure to the death of family members. Latinos, on the other hand, have modestly higher life expectancy than whites and much higher life expectancy than blacks. This suggests that Latinos may have similar exposure to the death of family members as whites and much less exposure than blacks, which may be important in the relatively favorable health profile of Latinos in the United States. The proposed project will shift thinking about racial/ethnic disparities and health by focusing on the death of family members throughout the life course as a fundamental cause of lifelong and accumulating disadvantage that affects long-term health and longevity. We hypothesize that the death of family members is more common and occurs earlier in the life course among blacks than Latinos and whites. In turn, death exposures shape the integrated biopsychosocial pathways that lead to poorer health and increased mortality risk, uniquely contributing to racial/ethnic disparities in physical health and mortality. We further hypothesize that these pathways will differ for men and women because of gender differences in family relationships, health outcomes, and potential mediating mechanisms such as health behaviors. This project relies on data from two NIH-sponsored national, longitudinal datasets (the Health & Retirement Study and the National Longitudinal Study of Adolescent to Adult Health) to estimate race/ethnic differences in specific (e.g., parents, children, siblings, spouses) and cumulative exposures to the death of family members across the life course, and how those exposures uniquely contribute to health from young adulthood to later life. Surprisingly little information is available concerning life course exposure to the death of multiple family members (and timing of deaths), and, in particular, racial/ethnic disparities in those exposures. The proposed project will provide the first in-depth and population-based analysis of race/ethnic differences in exposure to death of multiple family members from childhood through adulthood and how those exposures shape racial/ethnic disparities in health and mortality risk. This project is designed to produce a knowledge base that will inform specific and evidence-driven intervention and policy guidelines to address racial/ethnic disparities in health that result from exposure to death of multiple family members. The research team includes leading scientists who are nationally recognized in population health research. The team is characterized by a complementary set of talents and experience that uniquely positions them to carry out this innovative project.