Abstract Child maltreatment is a significant and costly social issue with over 670,000 documented cases annually. The effects of maltreatment are wide-ranging and include increased rates of morbidity and mortality from chronic diseases. To improve the health and mortality of this vulnerable population it is critical to delineate the pathways through which maltreatment contributes to increased risk for disease and identify opportunities for prevention. Dysregulation of the body’s physiological stress response systems constitutes a key pathway through which early maltreatment shapes biological aging processes and risk for subsequent disease. In addition, recalibration of the stress system during adolescence may mitigate the effects of early trauma on disease risk. Although the HPA axis in particular has been implicated as a key mechanism linking maltreatment with disease, these associations have only been tested between any two of these variables (i.e., maltreatment and HPA axis function, maltreatment and disease, or HPA axis function and disease) using cross-sectional or retrospective reports of maltreatment. This study will be the first to test this hypothesized mediation model from maltreatment to disease risk via HPA functioning using a developmental framework from childhood to young adulthood, incorporating multiple indices of disease risk. Second, the proposed work will be the first to use innovative new modeling techniques to characterize HPA axis functioning across four timepoints in adolescence to pinpoint the particular aspects of the stress response and developmental periods of stress system sensitivity that may lead to disease risk. Finally, this study will move beyond current conceptualizations of stress system dysfunction by identifying resilient profiles of HPA axis functioning and moderators of HPA axis recalibration that will provide critical new insights for intervention efforts focused on mitigating the effects of maltreatment on disease risk. The importance of assessing disease risk in young adulthood is bolstered by data indicating this period of life as a potential inflection point for long-term disease risk. As such, young adulthood may be a critical window for prevention and an optimal time to assess modifiable health risks. To accomplish this, we will leverage a unique prospective longitudinal dataset including youth with documented maltreatment histories and a comparison group from the same communities (90% minority race/ethnicity). This exemplary dataset will be augmented with follow-up assessment in young adulthood to capture disease risk. The findings will provide the first longitudinal evidence of HPA axis as a critical mechanism through which childhood maltreatment contributes to a lifelong trajectory of disease and whether recalibration of the HPA axis in adolescence can mitigate the effects of early trauma on disease risk in young adulthood. Identification of specific moderators of HPA axis recalibration can directl...