The majority of studies linking individual differences in the quality of social relationships and activity of the hypothalamic-pituitary-adrenal (HPA) axis have focused on the early development of attachment between infants and their caregivers. Later in development, during middle childhood and adolescence, the parallel HPA links to age-appropriate social relationships with peers, parents, and siblings remain largely unspecified. This study addressed this knowledge gap. Early morning saliva samples were obtained from 367 children in middle childhood (ages 6–10) and 357 adolescents (M age=11–16 years) on two successive days 1 year apart and assayed for cortisol. Latent state–trait modeling was employed to separate variance in cortisol levels attributable to “stable trait-like” versus “state or situational specific” sources to minimize the high moment-to-moment variation in basal adrenocortical activity. During adolescence but not middle childhood, and for girls but not boys, lower levels of “trait cortisol” were associated with poor quality social relationships. The pattern was robust, extending to the quality of relationships with parents, siblings, and peers. Importantly, the relationship was independent of the rates of internalizing or externalizing problem behavior. We found that isolating the variance in cortisol levels attributable to stable intrinsic sources revealed an interpretable pattern that linked individual differences in basal HPA activity to social relationships during adolescence. Studies are needed to reveal the biosocial mechanisms involved in the establishment of this gender- and age-specific phenomenon and to decipher whether or not individual differences in this hormone-behavior link are adaptive.