Anti-nucleosome antibodies, which recognise conformational epitopes consisting of histone and DNA in chromatin, have been described in autoimmune diseases. In this study, an attempt was made to isolate anti-nucleosome antibodies from the anti-DNA-depleted plasma IgG of two lupus patients either with or without nephritis by nucleohistone affinity chromatography. The purified nucleohistone-binding antibodies bound to nucleohistone in a specific manner and contained enriched anti-histone antibodies. However, adsorption of the purified antibodies with histone revealed that the nephritis patient-derived antibodies contained nucleohistone-specific antibodies. Although such purified antibodies may not recognise native structures of nucleosomes, this chromatography may provide a method to isolate and determine the fine specificity of anti-nucleosome antibodies in various autoimmune diseases.