Within two years of the recognition of autoantibodies to ribosomal P proteins in patients with systemic lupus erythematosus (SLE) an association with anti-P autoantibodies with psychosis was noted. While there has been some controversy about this association, ample evidence suggests a meaningful relationship between anti-P antibodies and central nervous system (CNS) disease. This evidence consists of 1) seven independent studies showing a strong relationship between anti-P antibodies and CNS disease; 2) longitudinal studies showing fluctuations of anti-P antibodies with episodes of psychosis; 3) correlation of anti-P antibodies with general disease activity; and 4) acid eluates form lupus renal tissue were found to contain anti-P antibodies enriched 30-fold with respect to their specific activity in serum heralding a direct role of anti-P antibodies in disease expression. Finally, there is evidence that the P protein resides on normal cells in an immunologically accessible way and evidence exists that anti-P antibodies are able to bind and penerate cells in culture, and once inside cells can affect a profound inhibition of protein synthesis in living cells. Taken together, these observations provide evidence linking anti-P antibodies to various forms of CNS disease. While this is true, there are other autoantibodies in SLE patients such as anti-dsDNA and antiglial fibrillary protein which may also play a role in the CNS disease of SLE patients. Continued study will inform us of the relative contribution of these autoantibodies to CNS disease in SLE patients.