Histological and clinical findings in 103 middle-aged patients suffering from diabetic glomerulosclerosis (gs) (biopsy material) are reported. In diabetic gs (as in other inflammatory and non-inflammatory glomerular disease) a statistically highly significant positive correlation exists between the grade of fibrosis of the renal cortical interstitium and the serum creatinine concentration at the time of biopsy. Rank correlations exist between vessel index and relative cortical interstitial volume on the one hand as well as serum creatinine concentration on the other. Significant differences are also shown to exist between the mean values of the cortical interstitium as well as the serum creatinine concentration and the vessel index in the four grades of diabetic gs. Severe glomerular lesions may be accompanied by a normal serum creatinine concentration, only if the interstitium shows no fibrotic changes. Mild glomerular lesions, when accompanied by an interstitial fibrosis, always have elevated serum creatinine concentrations. The incidence of hypertension, proteinuria, the nephrotic syndrome and hematuria in diabetic gs appears to vary greatly. From the highly significant correlation between the cortical interstitium and the serum creatinine concentration we presume the following: Alterations of the postglomerular vessels by interstitial fibrotic changes result in an increased resistance to renal cortical blood flow with a subsequent reduction of glomerular perfusion. This reduction of the glomerular perfusion may result in a rise of the serum creatinine concentration, independently of the severity of the glomerulosclerosis. It is also conceivable that glomerular function is affected by the malfunctioning atrophic tubules in areas of interstitial fibrosis.