Recent insights into the etiopathogenesis of nephritogenic immune responses are derived primarily from experimental models of systemic and organ-specific autoimmunity. Genetic analyses and immune-related gene ablation studies indicate that multiple independent mechanisms determine disease susceptibility. However, full characterization of proximal immunologic events in many diseases awaits identification of the renal antigens recognized by nephritogenic lymphocytes. Advances in characterization of effector mechanisms include epitope mapping of several putative pathogenic glomerular antigens and identification of novel pathways of immune-mediated tissue injury, including those involved in glomerular-tubulointerstitial communication and tubulointerstitial fibrosis. Finally, successful interruption of signal transduction pathways and transforming growth factor-beta 1 blockade by gene therapy suggest novel approaches to therapeutic intervention in immunologic renal injury.