The kidney is one of the major sites of EGF production and there it seems to play several biological functions, such as modulation of cell growth, renal repair following injury, regulation of cellular metabolism and glomerular haemodinamics. The present study was first aimed at localizing EGF and its receptor (R) in normal human kidney by immunohistochemical and in situ hybridization techniques. Then, the distribution of the growth factor and its R was explored in biopsy specimens from eight patients with acute tubulointerstitial damage. In the normal human kidney, both EGF immunoreactivity and EGF mRNA were localized in tubular profiles corresponding to Henle's loop and, although to a lesser intensity, to distal convoluted tubule. EGF immunostaining was remarkable mainly at the apical surface of tubular cells. EGF-R protein expression was detected in glomerular endothelial cells, in peritubular capillaries and arteriolar walls, as well as along the thick ascending limb of Henle's lop and distal convoluted tubule, where it colocalized with Tamm-Horsfall protein. Immunohistochemical analysis of tubular profiles revealed that EGF-R was located especially along the basolateral membrane of tubular cells and within the basal part of cytoplasm. Endogenous alkaline phosphatase and CHIP28 positive tubules did not show any signal for EGF and its receptor. Kidneys with acute tubulointerstitial injury exhibited a dramatic decrease of EGF expression, whereas EGF-R showed only minor modifications. Interestingly, EGF-R was localized to both apical and antiluminal membranes of positive tubular cells. It is concluded that EGF-EGF receptor loop may be relevant in the pathogenesis of acute tubulointerstitial damage and recovery from tubular injury, while its role in the physiological renewal of the urothelium remains speculative.