Antibodies against ribosomal phosphoproteins (anti-P antibodies) are found in about 10% of patients with systemic lupus erythematosus (SLE). Using an ELISA with a synthetic peptide for screening and an immunoblotting technique as a confirmation test for detection of these antibodies, we found 16 positive patients among 946 sera sent to our reference laboratory for anti-DNA determination. All 12 patients on which we could obtain clinical data had clearcut SLE, fulfilling 6 ARA criteria on average. Skin symptoms were observed more frequently in anti-P positive than in anti-P negative patients with SLE. We also tested 56 sera from 54 patients with well defined SLE during monosymptomatic exacerbations and found an identical frequency of about 10% of anti-P antibodies in groups of patients with different types of exacerbation, including psychosis. A retrospective analysis of 9 patients followed 3-10 years showed that they all were already positive for anti-P at the onset of disease. In total these patients showed 15 major peaks in anti-P levels (defined as at least a 4-fold rise in titer in a period of 3 months). Five of the fluctuations in anti-P levels were paralleled by fluctuations in anti-DNA levels. In 6/15 cases, peaks of anti-P levels were accompanied by an exacerbation of SLE, but only 2 peaks of anti-P levels were already detectable before the onset of the exacerbation. In addition, 6 other exacerbations occurred in the absence of major anti-P rises in the preceding 3 months. Therefore, quantitative determinations of anti-P have at most a limited practical value in the followup of patients with SLE.