Pressure natriuresis may be mediated through increases in inner medullary vasa recta blood flow (QVR). By means of acute renal decapsulation to prevent increases in renal interstitial hydrostatic pressure (RIHP), the effect of increases in QVRin the presence and absence of changes in RIHP in the natriuretic and diuretic responses to increases in renal perfusion pressure (RPP) was evaluated. Blood flow in descending (QDVR) and ascending (QAVR) vasa recta was determined in the exposed papilla by fluorescence videomicroscopy in anesthetized euvolemic Munich Wistar rats. In rats with intact renal capsules (n=12), increases in RPP from 101±0.5 to 132±2.9 mm Hg caused significant increases in QDVR(from 4.7±0.9 to 5.5±0.9 nl/min,p<0.001) and QAVR(from 2.8±0.2 to 3.5±0.2 nl/min,p<0.001) in association with increases in RIHP (from 4.6±1.3 to 7.6±1.3 mm Hg,p<0.001), urine flow (from 16.2±2.6 to 20.2±3.2 μl · min−1.g kidney wt−1,p<0.01), and urinary sodium excretion (from 2.10±0.38 to 3.36±0.62 μeq.min−1.g kidney wt−1,p<0.001). Acute bilateral renal decapsulation (n=12) prevented the rise in RIHP (from 4.0±0.6 to 3.6±0.6 mm Hg), urine flow (from 13.0±2.1 to 14.2±1.5 μl · min−1.g kidney wt−1), and urinary sodium excretion (from 1.76±0.28 to 2.12±0.31 μeq.min−1.g kidney wt−1) as RPP increased from 100±0.3 to 134±2.2 mm Hg but not the increases in either QDVR(from 4.4±0.5 to 5.1±0.5 nl/min,p<0.01) or QAVR(from 2.6±0.3 to 3.3±0.3 nl/min,p<0.001). No changes in QDVR, QAVR, RIHP, urine flow, and fractional excretion of sodium were observed in a third group of time control decapsulated rats (n=7) in which RPP was held constant at 100 mm Hg. Glomerular filtration rate and total renal blood flow were stable in all three groups. These findings demonstrate that QVRincreases in response to elevations in RPP but only results in natriuresis when associated with a concomitant rise in RIHP.