The immune system of normal unimmunized animals is characterized by the presence of B cells synthesizing and secreting mainly polyreactive, but also monoreactive, IgM and IgG natural antibodies that can react with a variety of self constituents. These antibodies, like the autoantibodies appearing in several immunopathological states, use the same genetic elements as the antibodies directed against environmental antigens, and seem to be encoded by unmutated germ-line genes. Accumulating evidence indicates that these natural auto-antibodies exert various biological roles, both related and unrelated to the immune system. In this article, Stratis Avrameas proposes that natural auto-antibodies, by interacting with the large number of self constituents present in an organism, establish an extensive dynamic network that contributes to the general homeostasis of the organism.