The participation of cell-mediated mechanisms in renal disease is reviewed. Experimental studies demonstrate that delayed-type hypersensitivity reactions can be elicited in the renal interstitium or in the glomerulus and produce lesions characterized by an influx of mononuclear cells and tissue damage. Methods for the analysis of cell-mediated reactions in tissue sections, especially those using monoclonal antibodies, are reviewed, and the possible role of cell-mediated mechanisms in human renal diseases is assessed. It seems probable that cell-mediated mechanisms are involved in the pathogenesis of certain forms of tubulointerstitial and glomerular disease, in particular, drug-induced acute interstitial nephritis, pyelonephritis, anti-GBM nephritis, and certain forms of acute glomerulonephritis. Conclusive evidence awaits, however, the development of techniques that permit identification of cell-mediated reactions in vivo.