The proximal tubule synthesizes and luminally secretes high levels of angiotensin II, which modulate proximal tubule transport independently of systemic angiotensin II. The purpose of this in vivo microperfusion study is to examine whether the renal nerves modulate the effect of intraluminal angiotensin II on proximal tubule transport. The decrement in volume reabsorption after addition of 10⁴ M luminal enalaprilat is a measure of the role of luminal angiotensin II on transport. Acute denervation decreased volume reabsorption (2.97 ± 0.14 vs. 1.30 ± 0.21 nl · mm¹ · min¹, P < 0.001). Although luminal 10⁴ M enalaprilat decreased volume reabsorption in controls (2.97 ± 0.14 vs. 1.61 ± 0.26 nl · mm¹ · min¹, P < 0.001), it did not after acute denervation (1.30 ± 0.21 vs. 1.55 ± 0.19 nl · mm¹ · min¹). After chronic denervation, volume reabsorption was unchanged from sham controls (2.26 ± 0.28 vs. 2.70 ± 0.19 nl · mm¹ · min¹). Addition of luminal 10⁴ M enalaprilat decreased volume reabsorption in sham control (2.70 ± 0.19 vs. 1.60 ± 0.10 nl · mm¹ · min¹, P < 0.05) but not with chronic denervation (2.26 ± 0.28 vs. 2.07 ± 0.20 nl · mm¹ · min¹). Addition of 10⁸ M angiotensin II to the lumen does not affect transport due to the presence of luminal angiotensin II. However, addition of 10⁸ M angiotensin II to the tubular lumen increased the volume reabsorption after both acute (1.30 ± 0.21 vs. 2.67 ± 0.18 nl · mm¹ · min¹, P < 0.05) and chronic denervation (2.26 ± 0.28 vs. 3.57 ± 0.44 nl · mm¹ · min¹, P < 0.01). These data indicate that renal denervation abolished the luminal enalaprilat-sensitive component of proximal tubule transport, which is consistent with the renal nerves playing a role in the modulation of the intraluminal angiotensin II mediated component of proximal tubule transport.