PROJECT SUMMARY/ABSTRACT Despite growing evidence that health outcomes are perpetuated across generations, empirical examinations of putative mechanisms underlying this intergenerational transmission are lacking. Explanatory mechanisms often focus on stress, which manifests in both psychological and physical symptoms. Relevant pathways have primarily been tested within a single generation or in non-human animal research. From mouse to man, evidence suggests that interplay across stress-related biological (e.g., cortisol, inflammation, telomeres) and psychosocial (e.g., social integration, health behaviors) factors critically contribute to the intergenerational transmission of health. The proposed study will examine the psychosocial ad biological mechanisms through which adversity transmits adverse mental and physical health outcomes across 3 generations and promotes the maintenance of health disparities. To this end, we will leverage a large (G1, n=1,630) and diverse (33% African-American) sample of older adults (currently aged 64-73) enrolled in an ongoing NIH-funded longitudinal study of stress and health and recruit their children (G2, n=2,200) and grandchildren (G3, n=1,900) to complete self-report questionnaires assessing stress, psychosocial factors, and health. From these, a subsample of 300 (150 Black and 150 White) G1/G2/G3 triads (total N=900) will visit our lab to provide blood and saliva measures so that we may assay the stress hormone cortisol, as well as inflammation markers. We will assay both their basal function and evoked activity. Triads and dyads will return to the lab 2.5 years later for a repeat assessment. All measures will be integrated with existing G1 data from our ongoing longitudinal samples. Investigating the intergenerational transmission of stress-related psychosocial and biological factors promises to inform our understanding of how health outcomes and racial health disparities are perpetuated across generations and, may, ultimately guide targeted prevention and public policy.