Idiotypes (Id) of human anti-DNA antibodies, designated as O-81 Id, were specifically detected on the immune deposits of renal glomeruli in 46% of patients with lupus nephritis. Id-binding to anti-Id antibodies was blocked by free O-81 Id and to some extent by free DNA. DNase or acid buffer treatment failed to reveal new Id determinants on the deposits. O-81 Id and NE-1 Id activity were also detected on the renal eluate-derived IgG, but not IgM from the autopsy cases with lupus nephritis. The incidences of O-81 Id were not associated with histological features in the glomeruli, but the distribution patterns were similar to those of IgG deposits. Our study also showed that 65% to 70% of patients with IgG deposits either in the subendothelium or in the subepithelial area of the glomerular basement membrane (GBM) showed positive tests for O-81 Id. It was also noted that most patients with massive proteinuria had O-81 Id in their glomeruli. It is concluded that O-81 Id deposits are relatively specific for active lupus nephritis and that immunofluorescence studies using anti-Id antibodies may be clinically useful for specifying the renal lesions of systemic lupus erythematosus (SLE).