Because of structural microheterogeneity, DNA can exert powerful effects that lead to immune system activation as well as antibody induction. These activating effects resemble those ofendotoxin and result from sequences that occur much more commonly in bacterial DNA than in mammalian DNA. In contrast, mammalian DNA can inhibit the response to bacterial DNA as well as other stimuli and may serve a counterregulatory role during infection. The recognition of the immune effects of DNA is relevant to the pathogenesis of a variety of infectious and inflammatory diseases including systemic lupus erythematosus, a prototypic autoimmune disease characterized by anti-DNA autoantibodies.