Autoimmune disorders occur more frequently in women. This predominance is attributed to gonadal steroids related to immunoactivation, fetal microchimerism and/or X chromosome inactivation. Both in vivo and in vitro experiments have shown that estrogen up-regulates humoral immune responses, which are suppressed by androgen and progesterone. The histopathological similarities between Scleroderma (SSc) and Graft versus host disease (GVHD) suggest its pathophysiology as chronic GVHD between fetal cells and maternal tissues. This hypothesis was confirmed using highly sensitive PCR and in situ hybridization. However, other reports have suggested that chimeric fetal cells can restore damaged maternal tissues. Finally, recent advances in molecular biology have revealed skewed X chromosomal inactivation in patients with autoimmune disorders. Females exhibit chimeric X chromosome activation status between Xp (paternal) and Xm (maternal) cells. If thymic antigen presentation cells become skewed for Xp or Xm, central T cell selection lacks Xp or Xm directed regulatory T cells. Other explanations suggest reactivation of silenced X chromosome and subsequent CD40L transcription and/or lack of pseudoautosomal region relatedimmunoregulation in Xo monosomy lymphocytes. From the evolutionary antiquity of sex over the acquired immune system, we suggest that viviparity is the ultimate cause of inconsistencies in autoimmune recognition.