Autoimmunity is controlled both by the environment and by genetic factors. One of the most well defined genetic factors is polymorphisms, with some alleles of particular genes promoting autoimmune diseases, whereas other alleles either not affecting susceptibility to disease or, in some cases actually inhibiting the appearance of such illnesses. Another genetically controlled factor, gender, also plays a profound role in the incidence of autoimmune diseases. For example, Systemic Lupus Erythematosus (SLE) occurs much more frequently in females than in males in both mice and man. The genetic differences that make some individuals susceptible to autoimmunity and protect others could act in many ways and affect many tissues. In this review we will discuss how gender may act on the cells of the immune system and thereby influence the predisposition of the host to autoimmune diseases.