Cytokines such as IL-1 and tumor necrosis factor alpha (TNF alpha) play a critical role in chronic joint inflammation and destruction. To study their regulation, we looked for circulating antiproinflammatory cytokine autoantibodies in 318 patients with chronic arthritis by immunoprecipitation with protein G. Anti-IL-1 alpha but not anti-IL-1 beta or anti-TNF alpha IgG antibodies were detected in 9% of blood donors and 18.9% of chronic arthritis patients. These antibodies were found more commonly and at a higher level in patients with nondestructive arthritis. Negative correlations were observed between the antibody levels and indices of disease activity and joint destruction. There was a negative association between the presence of anti-IL-1 alpha antibodies and that of HLA-DR4. These circulating anti-IL-1 alpha antibodies were not complexed with IL-1 alpha and could block specifically the biological activity of IL-1 alpha and its binding to membrane IL-1 receptors. These results indicate that these antibodies are beneficial, suggesting their contribution in the clinical presentation.