Rats immunized with renal tubular antigens were protected from the development of interstitial nephritis by pretreatment with tubular antigen-reactive T lymphoblasts. Protected animals developed anti-idiotypic antibodies against idiotypes primarily within the antigen-binding region of monoclonal antitubular basement membrane antibodies. These studies extend the concept of auto-anti-idiotypic regulation to autoimmune disease, and they also provide an experimental basis for further efforts to develop biologically relevant mechanisms for attenuating the expression of other kidney diseases.