The disease systemic lupus erythematosus (SLE) is a complex one. One major clinical manifestation that relates to both cause and pathogenesis of all autoimmune diseases but specifically SLE is the sexual predilection for females. A consideration of mechanisms for this manifestation is the subject of this paper. The cytokine network is a major aspect of immune regulation and directly affected by sex steroids. The sexual dimorphism of the immune system relates to both organ-specific and general synthesis of sex steroids that are affected by and in turn affect cytokine profiles of T helper cells. There are also specific responses in cells from diseased patients that support the molecular activities of sex hormones on cells. Among these is the rise of calcineurin mRNA in SLE T cells in response to estrogen. Clinical research provides support for a more estrogenic environment in patients with SLE of both sexes. A preferential hydroxylation of estrone and increased oxidation of testosterone in patients with SLE maximizes the effects of estrogens on T cell functions. The effects of gonadotrophins like prolactin are discussed as stimulants of immune functions when elevated in SLE. Last, while the roles of exogenous estrogens on immune functions are known, the effects of such steroids alone or in combination with progestogens on SLE are not known. Investigation of both hormone replacement therapy and premenopausal hormone use are in progress.