Autoimmunity results from a breakdown of physiological mechanisms responsible for maintaining tolerance to self-antigens. These mechanisms are traditionally divided into central and peripheral. T or B lymphocytes that bind to self-antigens with high avidity are deleted or rendered unresponsive during their ontogeny in generative lymphoid organs such as the thymus and the bone marrow (central tolerance). However, this elimination process is incomplete, and regulatory mechanisms that keep mature autoreactive lymphocytes in check are necessary for preventing autoimmunity (peripheral tolerance). Peripheral tolerance mechanisms include passive or activation-induced T and B cell apoptosis, anergy, ignorance, and perhaps suppression of autoreactivity by regulatory lymphocytes. Observations in humans and experimental animals with defined genetic mutations provide examples of autoimmune disorders arising from failure to maintain peripheral tolerance to self. However, multiple factors are necessary for the induction of autoimmunity. For example, bacterial and viral infections may precipitate autoimmune disease in genetically susceptible individuals by exposing autoreactive T cells to cross-reactive peptides (molecular mimicry) or by enhancing lymphocyte stimulation.