--- - |2 The Biobehavioral Family Model (BBFM) is a biopsychosocial model of health. This model proposes that biobehavioral reactivity mediates the association between the family emotional climate and disease activity. To improve the clinical relevance of the BBFM, variables that mediate the association between family emotional climate and biobehavioral reactivity need to be tested. This study examined differentiation of self as a mediator. Using data from the Midlife Development in the United States study (n = 854), results suggested that differentiation of self mediated the association between the family and intimate partner emotional climate and mental health symptoms. These findings suggest that including differentiation of self into the BBFM may help interventions based on the model target factors that could improve health outcomes. - Journal of Marital and Family Therapy, EarlyView.