The complexity of the intrarenal renin-angiotensin (Ang) system (RAS) continues to reveal itself as evidence accumulates demonstrating its robust independent regulation in the interstitial and intratubular compartments within the kidney. 1–3 Early reports demonstrating the presence of Ang II receptors on the brush border of proximal tubules suggested physiological roles. 4 However, because of the abundance of degradating enzymes on the brush border, the concentrations of angiotensin peptides were considered to be relatively low. Nevertheless, the abundance of luminal Ang II receptors throughout proximal and distal nephron segments sustained interest in the luminal actions of Ang II. 5, 6 Tubular perfusion studies indicating that luminal Ang II alters tubular sodium and volume reabsorption rate1, 5, 7, 8 supported an important physiological role for luminal Ang II receptors. 9 A paradigm shift occurred when it was discovered that the proximal intratubular concentrations of Ang I and II were much greater than their corresponding plasma concentrations. 7, 10, 11 In addition, when proximal tubular fluid was incubated with excess renin, the resultant formation of Ang I indicated very high angiotensinogen (AGT) substrate availability in this segment. 7, 12 Furthermore, tubular fluid collected from downstream segments of perfused tubules also had Ang II concentrations similar to those in nonperfused tubules, thus supporting a local origin. 11 These findings, along with the demonstration that proximal tubule cells express AGT mRNA and protein, 13, 14 established the foundation for the existence of a robust physiologically important tubular RAS.