Neutralizing autoantibodies to interleukin (IL)-1 alpha were detected in a subset of chronic polyarthritis patients characterized by an increased proportion of patients with primary Sjögren's syndrome or self-limiting inflammatory arthritis, diseases with a much better prognosis than rheumatoid arthritis (RA). The evolution of anti-IL-1 alpha antibody levels was followed over 3 years. Incidence and levels were higher in patients with a benign form of polyarthritis. In these patients levels remained stable or increased over the follow-up period. In contrast, incidence and levels were lower and some RA patients became negative. Negative correlations were observed between the levels of anti-IL-1 alpha antibodies and the clinical and biological indices of disease activity. The relative risk factor of developing RA was 12 in the absence of high anti-IL-1 alpha antibody levels and 18.2 when associated with the presence of HLA-DR4. In conclusion, the presence of anti-IL-1 alpha autoantibodies appears to be protective and their detection could represent a marker of good prognosis for destruction.