The frequency and clinical significance of anti-RNP antibodies in patients with systemic lupus erythematosus (SLE) are still a matter of debate. In this study we report our experience with a series of 123 unselected Italian patients (93 adults and 30 children) suffering from SLE according to the ARA criteria. Anti-RNP were detected by counterimmunoelectrophoresis in 25 patients (20%), 19 of whom did not show other antibodies to extractable antigens (isolated RNP). Our study shows a striking association between anti-RNP and arthritis as well as between anti-RNP and Raynaud's phenomenon. In addition, we found an association between anti-RNP and lack of renal involvement. This association was limited to those patients with isolated RNP and was independent of the presence of anti-dsDNA antibodies. These data were confirmed by a 50 month follow-up study.