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Abstract: Background/Objective: Detection of anti-nucleosome antibodies in patients with systemic lupus erythematosus (SLE) has been well established and it is claimed that their presence is associated with disease activity. The objective of this study is to determine the diagnostic value of anti-nucleosome antibodies in the assessment of lupus nephritis and clinically active SLE. Methods: The anti-nucleosome antibodies were evaluated in the serum of 200 Tunisian SLE patients at disease onset by a sensitive immunodot assay. Serum samples from each patient were also tested for ANA and anti-ds DNA antibody by IIF on Hep 2 cells and Crithidia luciliae respectively. During the follow-up, the patients were regularly monitored for clinical parameters. Global SLE activity was measured by the European Consensus Lupus Activity Measurement (ECLAM). Results: The prevalence of anti-nucleosome and anti-dsDNA antibodies was 69% and 63.5% respectively. Anti-nucleosome antibodies were found to be 30.1% positive in SLE patients lacking anti-dsDNA antibody. 79.5% patients had active SLE at the first clinical examination. Anti-nucleosome antibodies were more sensitive than anti-dsDNA antibodies to detect active SLE (78%vs. 71.7%, P =0.19). 52.5% of SLE patients had renal involvement. Among these patients, the rate of anti-nucleosome positivity and anti-dsDNA were 77.1% and 67.6% respectively. The positivity of anti-nucleosome antibodies was significantly higher in patients with renal disease than the subjects without renal disease (P = 0.009). Anti-nucleosome and anti-ds DNA antibodies were significantly correlated with disease activity (P < 0.001 and P < 0.001 respectively). Conclusion: Anti-nucleosome antibody reactivity may be a useful marker in the diagnosis and assessment of active SLE. [Copyright &y& Elsevier]