Linking Biological and Social Pathways to Adolescent Health and Well-Being Abstract Research across disciplines provides strong evidence that exposure to chronic stress contributes to poor physical and mental health outcomes across the life course. Consequently, large-scale population studies have increasingly integrated the collection of biomarkers of hypothalamus-pituitary-adrenal (HPA) activity (e.g. cortisol) to investigate the extent to which the neuroendocrine pathway explicates the role of chronic stress in shaping poor health outcomes and racial/ethnic and socioeconomic health disparities. However, few population studies have collected cortisol biomarkers from adolescents and among those that have, significant methodological challenges ultimately hampered data quality. Therefore, the purpose of this R21 proposal is to field test the collection of non-invasive longitudinal cortisol samples from adolescents to explore the validity and reliability of nightly measures of salivary cortisol for 6 nights and one hair sample for cortisol. The findings will determine if the collection of these measures is feasible and informative in a population of adolescents across a spectrum of social risk for impaired health. This R21 proposal is unique in that we will leverage a subsample of adolescents participating in the first wave of a recently funded prospective cohort study - the Adolescent Health and Development in Context (AHDC) study (PI Browning; NIH 1R01DA032371-01 and the William T. Grant Foundation). The AHDC study will examine the impact of spatial and social exposures on the risk behavior, victimization and mental health outcomes of 4,000 adolescents aged 11-17 years in Franklin County, Ohio. The specific aims of this R21 proposal are: Aim 1: To field test the collection of non-invasive biomarkers of cortisol in adolescents via nightly salivary samples for 6 nights and one hair sample and Aim 2: To examine the relationships between the (a) cortisol biomarkers; (b) immune function biomarkers (EBV DNA) and (c) linked secondary data from the AHDC study of adolescent risk behavior, psychosocial stressors, and environmental stressors. Our analytic strategy will employ advanced multilevel modeling techniques designed to estimate the variability in cortisol levels between and within individuals and the behavioral, psychosocial and environmental stressors associated with this variability. The findings of this R21 proposal will inform the selection of a high-quality, feasible and cost-effective biomarker data collection protocol to determine the biological impact of social risk on adolescent health and behavior in the second wave of the AHDC study. In addition, these data will inform the design of future population research studies to reduce adolescent health risk and disparities, with potential health benefits over the life course.