The pathogenicity of highly purified brush border membrane (BBM) antigens in Heymann Nephritis was compared to that of a crude renal tubular Fx1A preparation and was found to be equally pathogenic. Both antigen preparations induced formation of autologous antisera. Double immunodiffusion studies demonstrated a reaction of identity between anti-BBM and anti-Fx1A antisera. Both antisera detected the same number of antigenic components when reacted against BBM or Fx1A preparations. When antibody was eluted from the kidneys of rats with Heymann nephritis it reacted in vitro with the renal BBM as shown by indirect immunofluorescence. Eluted antibody also cross reacted with epididymal tubules, but not with other epithelia, showing that the pathogenic antigens have a restricted tissue distribution. Heymann nephritis was readily induced in rats, but could not be induced in dogs, suggesting a species difference in susceptibility to this form of nephritis. Injection of heterologous anti-BBM or anti-Fx1A antisera resulted in rapid localization to the GBM in a granular pattern, suggesting reaction with circulating antigen or in situ immune complex formation with native or planted glomerular components. Rats with aminonucleoside nephrosis showed BBM localization of injected heterologous antisera, demonstrating their specificity in vivo. Our data provide a rationale for using purified BBM antigens for the production of a homogeneous model of Heymann nephritis.