The pleiotropic cytokines, interleukin (IL)-1 alpha, type I interferons and IL-6 also act on cells involved in antibody production. Somehow the immunologic tolerance to these cytokines is often spontaneously broken--even in healthy individuals. Thus, relatively high concentrations of high affinity IgG antibodies against IL-1 alpha and IL-6 frequently occur in the circulation of healthy adults. The autoantibodies specifically antagonize the respective cytokines in vitro. Thermodynamic estimations strongly suggest that autoimmunity can play a significant role in the regulation of certain cytokines. In the light of IL-6 autoantibodies the possible biological and clinical significance of cytokine autoimmunity is discussed.