Systemic lupus erythematosus (SLE) is a prototype systemic, autoimmune inflammatory disease that can involve virtually any organ or tissue type. The disease has a strong familial tendency but, like most human illness, has a complex pattern of inheritance that is consistent with multiple susceptibility genes as well as environmental risk factors. Association studies have been performed, especially for the major histocompatibility complex on chromosome 6 and for various complement components. Several large familial studies have begun to report results for genetic linkage. Linkage has been established for many genetic intervals. SLE is a complex clinical illness, and investigation of the genetics of the illness based on clinical manifestations revealed linkages not found without consideration of the phenotype of the disease.