Tubulointerstitial nephritis (TIN) describes a range of pathological processes that are at least partly responsible for the progression of renal disease of nearly all aetiologies. TIN is frequently the most important pathological manifestation of progressive glomerulonephritis, obstructive uropathy, reflux nephropathy and cystic diseases, although it may also present as a primary disease process associated with infection, drug use or other immunologically mediated disease. Recent clinical and laboratory research has increased our knowledge of tubulointerstitial structure, physiological function and tubulointerstitial response to injury. This review presents a classification of TIN in which acute and chronic tubulointerstitial diseases are recognized as forming a continuum. Primary TIN and TIN associated with glomerulonephritis, obstructive nephropathy and chronic progressive renal disease are discussed from both clinical and pathogenic aspects. It is argued that chronic TIN is a disease process in which inflammation is accompanied by a destructive tubulopathy and fibrogenesis. In acute TIN there is a cessation and reversal of this process. It is suggested that most forms of TIN have an immunological basis because of the presence of immune cell infiltrates, the occurrence of TIN in several immune diseases and immunological animal models of TIN. However, to date TIN has not been convincingly modified in patients by immune manipulation. Experimental evidence suggesting an important pathogenic role for proteinuria and antigenuria, and the renal tubule cell acting as an antigen-presenting cell is discussed.