Oxytocin appears to be centrally involved in socioemotional functioning, and is hypothesized to be relevant to the severe disruption in close relationships characteristic of borderline personality pathology. We examined whether a polymorphism of the oxytocin receptor gene (OXTR rs53576) interacts with quality of family functioning to predict borderline personality disorder (BPD) symptomatology in a sample of youth at age 20. A total of 385 youth from a longitudinal study of offspring of depressed or nondepressed mothers who were well characterized with respect to their family conditions and BPD symptomatology provided DNA for genotyping. Analyses revealed a significant moderation of the link between early family quality and later BPD symptoms by OXTR rs53576, and the pattern was consistent with differential susceptibility (plasticity). Whereas A-allele carriers had high levels of BPD symptoms under negative family conditions and low levels under positive conditions, GG homozygotes had average levels of BPD symptoms regardless of their family quality.