Bidirectional cell transfer during pregnancy frequently leads to postpartum persistence of allogeneic cells and alloimmune responses in both the mother and in her offspring. The life-long consequences of naturally acquired alloimmune reactivity are probably of importance for the outcome of allogeneic stem cell transplantation. We investigated the presence of CD8^pos minor histocompatibility (H) antigen–specific cytotoxic T lymphocytes (T_CTL) and CD8^pos minor H antigen–specific T regulator cells (T_REG) in peripheral blood cells obtained from 17 minor H antigen–disparate mother-offspring pairs. Absence of minor H antigen–specific T_REG, as marked by the feasibility to expand T_CTL from isolated tetramer^pos populations, was observed in 6 mothers and 1 son. The presence of minor H alloantigen–specific T_REG was observed in 4 mothers and 5 sons. These T_REG were detected within isolated tetramer^dim staining fractions and functioned in a CTLA-4–dependent fashion. Our study indicates that both T_CTL and T_REG mediated alloimmunity against minor H antigens may be present in healthy female and male hematopoietic stem cell donors, potentially influencing graft-versus-host reactivity in different ways.