In this study we evaluated the presence of anti-nucleosome reactivity in children with systemic lupus erythematosus (SLE), and assessed its clinical correlations in comparison with anti-dsDNA and anti-histone IgG levels. Reactivities to nuclear substrates were determined by enzymatic immunoassays in 80 sera from 22 children with SLE, and solid phase adsorption experiments were performed. In children with active SLE, the anti-dsDNA, anti-histone, and anti-nucleosome IgG levels were elevated, and were significantly correlated with disease severity; during remission anti-histone (but not anti-dsDNA and anti-nucleosome) antibodies, although reduced, were still significantly elevated. The results of adsorption studies showed that anti-dsDNA antibodies contributed to anti-nucleosome reactivity, while anti-histone antibodies did not. The recognition of the H3H4-DNA nucleosome subparticle, rather than H2AH2B-DNA, may be related to the nucleosome reactivity. In children with SLE anti-nucleosome reactivity is present; it is in part due to anti-dsDNA antibodies and in part to antibodies recognizing conformational epitopes that may be related to the H3H4-DNA nucleosome subparticle. Its clinical significance for diagnosis is not greater than that of the anti-dsDNA antibodies.