IgG antibody specific to double-stranded DNA (dsDNA) has been recognized as a predictive indicator of the renal involvement in systemic lupus erythematosus. However, we recently experienced two cases of overt lupus nephritis without IgG anti-dsDNA antibody. In both cases, high titers of antibody to the histone dimer (H2A-H2B)-dsDNA complex were detected. They responded well to the corticosteroid therapy, with a cytotoxic agent in one case, and the titers of anti-(histone-DNA) antibody was decreased along with the improvement of proteinuria. Based on the recent reports suggesting a pathogenic role of this antibody in lupus nephritis, we suggest that measurement of the anti-(histone-DNA) antibody is necessary in lupus nephritis patients, especially when IgG anti-dsDNA antibody is not detectable.