Lupus glomerulonephritis is frequent and occurs in over 50% of patients with clinical evidence of systemic lupus erythematosus (SLE). It is generally accepted that lupus glomerulonephritis results from the deposition or the in situ formation of DNA/anti-DNA immune complexes in the kidney. However, circulating DNA/anti-DNA immune complexes have been found in only a minority of patients, no convincing data have been provided by experimental study in animals, and the demonstration of DNA in glomerular deposits remains questionable. Immunochemical properties of murine and human monoclonal anti-DNA antibodies suggest new pathogenic mechanisms for anti-DNA antibodies: their direct binding to a glomerular structure sharing an epitope with DNA. This hypothesis needs to be demonstrated in SLE patients and in experimental models.