In Part II of his review of the basis of autoimmunity, Argyrios N. Theofilopoulos summarizes current knowledge on the genetic factors that contribute to autoimmune disease predisposition. The findings indicate that multiple genes contribute to the induction of pathogenic autoimmunity, and that no single genetic abnormality is sufficient in itself to induce disease. The definition of these genetically complex diseases is about to be revolutionized by the development of genome scanning approaches, such as dense chromosomal maps based on polymorphic microsatellite DNA and other informative markers. These will allow the loci and genes that predispose to these diseases to be identified broadly.