We studied the relative role of anti-DNA antibodies in pathogenesis of murine lupus nephritis, and we used, as index of their contribution, the association between attenuation, or progression, of renal disease and decrease or increase in concentration of anti-DNA antibodies in the plasma and renal eluate of NZB/W mice. The concentration of anti-DNA antibodies in plasma did not discriminate mice with incipient or drug attenuated nephritis, who had normal renal function, from mice with progressive nephritis, who developed renal failure. Although the quantity of IgG eluted from kidneys reflected the extent of renal disease (mice with progressive nephritis greater than mice with attenuated nephritis greater than mice with incipient nephritis), the anti-DNA activity of such antibodies was negligible. The low anti-DNA activity could not be attributed to either excess DNA or DNAase in renal eluates. In fact, the eluates contained a factor that inhibited the interaction between anti-DNA antibody and DNA. The results indicate that immune complex systems other than, or in addition to, DNA-anti-DNA are likely to play a role in the pathogenesis of murine lupus nephritis.