This paper describes the clinical significance of antibodies to the ribosomal P proteins in systemic lupus erythematosus. It appears that liver disease due to the lupus process and not attributable to viral infection, alcohol or drugs is associated with anti-ribosomal P. In addition, there is a strong relationship to central nervous system disease and nephritis of antibodies to ribosomal P proteins. The prevalence of the anti-P antibodies is strongly related to disease activity wherein disease remission is associated with disappearance of anti-P antibodies. These phenomena taken together suggest an immunopathogenic role for anti-P antibodies. This idea is strongly supported by the observation that immunoglobulin G containing antiribosomal P activity binds and penetrates living cells with profoundly inhibitory effects on protein synthesis. Finally, a new era of research has been uncovered by the observation that in 54 of 55 instances normal sera passed over a ribosome-sepharose column unmasks anti-P antibodies, which can be eluted from the ribosome column with 3.0 M magnesium chloride. This suggests that anti-idiotypes regulate the expression of anti-P antibodies in normal persons and in lupus patients this regulation is ineffective, with the development of free anti-P antibodies in a proportion of patients with active disease.