The aim of this study was to test the hypothesis that the intrarenal renin-angiotensin system (RAS) modulates glomerular angiotensin II (ANG II) receptors. In one protocol ANG II receptors were measured 7 days after unilateral denervation of the left kidney in rats. There were 50% more receptors in the glomeruli from denervated compared with innervated kidneys (right, 1,037 +/- 108 vs. left, 1,556 +/- 143 fmol/mg; P less than 0.01), which was associated with a 63% reduction (P less than 0.01) in left renal vein renin. The differences in ANG II receptors between the left and right kidneys were no longer present when angiotensin-converting enzyme was inhibited with enalapril or when pharmacological amounts of ANG II (50 ng/min) were infused. In a second protocol, renal cortical renin content was raised in the left kidney by placing a 0.20-mm clip on the left renal artery (two-kidney, one-clip Goldblatt model). At 7 days, glomerular ANG II receptors were reduced by 72.3% in the clipped compared with the contralateral kidneys (right, 1,232 +/- 105 vs. left, 341 +/- 170 fmol/mg; P less than 0.01). The differences in ANG II receptors were no longer present after enalapril treatment. Pharmacological maneuvers that either blocked ANG II formation or increased circulating ANG II resulted in an equal number of ANG II receptors in the right and left kidneys. The data indicate that the intrarenal RAS modulates the density of glomerular ANG II receptors and is a more important receptor modulator than plasma ANG II.