Abstract On average, the mothers of children with serious conditions (e.g., mental illnesses, disabilities, developmental disorders, chronic conditions) face health risks due to caregiving burdens, stress, and other factors that often counter the many rewarding aspects of their parenting. These health implications appear to be magnified when children reach adulthood and mothers reach late midlife and beyond. Modern medical and therapeutic advances have increased the number of mothers in this vulnerable position, and they need support. This project will further build the theoretically grounded empirical foundation for that support by employing an innovative life course approach and mixed methods strategy to address this significant public health issue. Specifically, this project extends and enriches the literature on the physical and mental health of mothers of children with serious conditions by asking three questions. The first question (“why?”) concerns the complex ways that the social and psychological rewards and strains of parenting children with serious conditions into adulthood converge to shape mothers’ health in late midlife. The second question (“when?”) concerns the potential for cumulative vs. sensitive periods of risk and resilience across years of caring for children with serious conditions from their births into their adulthoods. The third question (“where?”) concerns the degree to which family supports in the informal ecology and community health and human services in the formal ecology moderate the exchange of rewards and strains to buffer health risks among late-midlife mothers of young adult children with serious conditions. These questions will be addressed with a sequential explanatory mixed methods strategy in which quantitative results are unpacked by qualitative insights and qualitative insights guide subsequent quantitative analyses. This strategy integrates statistical analyses of an extant population database with textual/grounded theory analyses of newly collected qualitative data, both focusing on mothers in the sixth decade of life. The first involves approximately 3,100 mothers of young adult children (420 of whom had serious conditions) in the geocoded, multilevel National Longitudinal Survey of Youth 1979. The second involves 80 mothers of young adult children with and without serious conditions. This mixed methods sequence is already vetted and supported by preliminary analyses of the quantitative data published in a high-impact journal and a smaller-scale qualitative data collection funded by an NIA pilot mechanism. Conducted by an interdisciplinary team of senior and junior scholars with complementary expertise in the study of families and health, this project will put forward and refine a life course framework of health and wellbeing in the context of the indefinite responsibilities of intensive parenting that can guide future research in this area and help to tailor policies and programs aiming to serve this ...