The aim of this study is to investigate the prevalence of anti-nucleosome antibodies in systemic lupus erythematosus and their association with disease activity and renal involvement. Fifty SLE patients of a mean age of 28 years and mean disease duration of 5.46 years were subjected to full history taking, full clinical examination, serum ANA, anti-dsDNA and anti-nucleosome antibodies, with thirty healthy adults served as a control group. A highly significant correlation was found between patients and control as regards the prevalence of anti-nucleosome antibodies. A non-significant difference was detected between the presence of anti-nucleosome antibodies and the nephritis. Anti-nucleosome antibodies are present with a very high frequency in SLE but no association with disease activity or renal involvement could be detected.