Research suggests that the pubertal transition, particularly when experienced earlier than age-matched peers, is associated with heightened depression in girls but less depression in boys. This study examined whether stress within other-sex relationships serves as one process through which puberty differentially contributes to depression for girls and boys. Youth (51 girls, 34 boys; M age = 12.68) and their caregivers reported on pubertal status and age of menarche. Semistructured interviews were conducted to assess youths' depression and exposure to chronic other-sex stress. As anticipated, more advanced status and earlier timing were associated with more depression in girls and less depression in boys. More advanced status and earlier timing were associated with less other-sex stress in boys; earlier age of menarche was associated with more other-sex stress in girls. Other-sex stress partially mediated the early menarche-depression association in girls, suggesting one process through which puberty promotes risk for depression in girls. (Contains 4 tables and 3 figures.)