The aim of the present study was to investigate and quantitate the structural renal changes developing after stenosis of the renal artery. Twelve kidneys removed at operation from patients with elevated blood pressure due to stenosis of the renal artery were investigated together with three kidneys with renal artery stenosis but no clinical evidence of renovascular hypertension. Eight age-matched autopsy kidneys served as controls. Stereologic methods were used to estimate the volume fractions of different structural parameters, the volume of individual glomeruli, and the structural integrity between the glomerulus and the proximal tubule. In six of the kidneys with renal artery stenosis and in the controls, the total number of nonoccluded glomeruli was estimated. Immunohistochemical staining for epithelial membrane antigen, Tamm-Horsfall protein and lectin Arachis hypogaea was performed in order to determine whether the atrophic tubules in renal artery stenosis were of proximal or distal origin. The results showed that the volume fractions of both proximal and distal tubules had decreased in renal artery stenosis, whereas the volume fractions of the glomerular tufts and interstitium increased. Immunohistochemical staining indicated, however, that more distal than proximal tubules were preserved, although atrophic. In the kidneys with artery stenosis, very few glomeruli were seen connected to a normal proximal tubule; in 52% of the glomeruli Bowman's capsule did not open toward a tubule and 40% were connected to an atrophic tubule. The mean glomerular volume (uncorrected for shrinkage) of 1.5.10(6) microns3 in the kidneys with artery stenosis was significantly decreased compared with the 2.9.10(6) microns3 in the controls. The mean glomerular number was normal in the kidneys with artery stenosis. The study shows that despite the absence or severe atrophy of the tubules, the glomeruli are not destroyed but only smaller. More proximal than distal tubules are destroyed by the ischemic process.