The degree of impairment of renal function in patients with chronic renal failure correlates closely with the extent of fibrosis in the tubulointerstitium, i.e. of interstitial extracellular matrix (ECM) accumulation. The composition of this pathological extracellular matrix and the relation between the ECM composition on the one hand and the severity of histological changes and renal function on the other has not been investigated. This prompted us to perform the present study. The severity of histological abnormalities and the composition of the interstitial ECM were assessed using a semiquantitative scoring technique in 57 biopsies from patients with kidney disease of diverse etiology and variable degrees of renal failure and were contrasted with the results of 9 control biopsies. Tissue sections were stained with an indirect immunoperoxidase technique using antibodies against collagen I, III, IV, V, VI, laminin, fibronectin, decorin and heparansulphate proteoglycan core protein (HSPG). Collagen IV, laminin and HSPG were virtually absent from the interstitium in controls. These components were more widely distributed in patients and the extent of their deposition correlated with the severity of interstitial histological abnormalities. In patients with severe interstitial damage the deposition became diffuse. Collagen type I and III were already diffusely distributed in the interstitium of controls and did not increase significantly as interstitial damage became more severe. However, the extent of collagen III staining in patients was significantly higher than in controls. Decorin staining showed a patchy distribution both in patients and controls. The overall distribution was significantly increased in patients. The extent of the deposition of both collagen V and VI was significantly increased in patients when compared with controls. Only the distribution of collagen V correlated with the severity of histological abnormalities. Our findings suggest that an increased interstitial deposition of extracellular matrix substances which are generally regarded as basement membrane components contributes more to the development of interstitial fibrosis and renal failure than the deposition of the fiber forming interstitial collagens type I and III, which are prominent in controls and in patients irrespective of the severity of histological abnormalities. Decorin staining was significantly enhanced in patients and was found to be the best predictor both of the severity of interstitial fibrosis and of renal failure. This could mean that decorin is important in human renal pathology. Collagen V and VI staining was significantly increased in patients when compared with controls. To our knowledge this is the first study in which this is demonstrated.