This study was addressed to explore the reactivity of natural anti-idiotypes from commercial lots of immunoglobulins to several idiotypes (Ids), usually expressed by anti-DNA molecules in lupus nephritis. Eleven intravenous immunoglobulin (IVIG) preparations and nine (three polyvalent and six hyper-immune) intramuscular IgG were investigated for specific content of anti-DNA, anti-F(ab')2 and antibodies reacting with several anti-DNA IgG Ids. Two samples (nos 6 and 11) showed high reactivity with allogeneic F(ab')2 and with F(ab')2 of myeloma proteins bearing the anti-DNA Id 3I+ and the 8.12+. Since both 3I and 8.12 Id markers are known to characterize pathogenic anti-DNA IgG in systemic lupus erythematosus (SLE), anti-Id antibodies to these markers were obtained by absorbing the IVIG samples nos 6 and 11 to Sepharose columns coupled with pooled F(ab')2 fragments of 3I(+)-F4(+)-8.12(+)-myeloma proteins. Inhibition experiments showed that anti-8.12 Id-eluted IgG induced a selective suppression of the DNA-reactive antibodies derived from patients with active lupus nephritis to their substrate, suggesting the involvement of 8.12+ molecules in the SLE glomerular damage. Since 8.12+ anti-DNA are nephritogenic antibodies, the occurrence of anti-8.12+ Id in commercial IVIG may be of potential therapeutic relevance in modulating the pathogenic SLE Id network. Previous variable results of IVIG treatment in SLE, such as resolution of proteinuria or worsening nephritis, could be related to variable enrichment of different lots of IVIG in suppressive anti-pathogenic Id antibodies.