A growing body of evidence indicates that children reared in harsh families are prone to chronic diseases and premature death later in life. To shed light on the mechanisms potentially underlying this phenomenon, we evaluated the hypothesis that harsh families engender a proinflammatory phenotype in children that is marked by exaggerated cytokine responses to bacterial stimuli and resistance to the anti-inflammatory properties of cortisol. We repeatedly measured psychological stress and inflammatory activity in 135 female adolescents on four occasions over 1.5 years. To the extent that they were reared in harsh families, participants displayed an increasingly proinflammatory phenotype during the follow-up analyses. This phenotype was marked by increasingly pronounced cytokine responses to in vitro bacterial challenge and a progressive desensitization of the glucocorticoid receptor, which hampered cortisol's ability to properly regulate inflammatory responses. If sustained, these tendencies may place children from harsh families on a developmental trajectory toward the chronic diseases of aging.