The role of a functional renal papilla in renal interstitial hydrostatic pressure (RIHP) response to saline volume expansion (SVE, 5% bw, ~ 30 min, 0.9%) was assessed in male rats pretreated with either 0.9 % saline (CTR, 200 µl, i.a.) or 2‐bromoethylamine (BEA, 200 mg/kg, i.a.). After 7 days, RIHP (subcapsular, mmHg), renal cortical and medullary blood flows (RCBF/RMBF, L‐D, APU), urinary water (V, ml/ min/ 100 g bw), sodium (UNaV, µEq/ min/100g bw) and nitrogen oxides excretions (UNOxV, Griess, nmol/min/100g), Ht (%) and [Pr]p (g%) were measured in anesthetized animals with hormonal clamp, kidney denervation and renal perfusion pressure control at 100 mmHg (CTR: n = 9, bw = 345 ± 7 g, Uosm = 1940 ± 187 mOSM vs. BEA: n = 12, bw = 303 ± 9α g, Uosm = 371 ± 43α mOSM) during hydropenia (H), SVE, and maintained SVE (mSVE). The results are mean ± SEM. α p<0.05 between groups in the same period, * p < 0.05 vs. H in the same group. CTR BEA H SVE mSVE H SVE mSVE Ht 51.3±0.4 45.0±*0.9 44.2±*0.8 52.6±0.7 44.0±*1.0 44.0±*1.2 [Pr]p 5.1±0.2 3.2±*0.1 2.8±*0.2 5.2±0.2 3.3±*0.2 3.2±*0.2 RIHP 4.2±0.3 27.2±*4.3 26.0±*4.8 4.1±0.6 26.0±*1.5 26.0±*2.2 UNOxV 0.46±0.1 1.8±*0.4 2.7±*0.6 0.44±0.1 1.8±*0.5 2.6±*0.7 RMBF 431±89 464±101 473±95 178±Î±54 249±Î±54 283±Î±65 UNaV 0.019±0.005 1.07±*0.16 2.53±*0.42 0.20±Î±0.06 0.86±*0.12 1.56±Î±*0.16 Conclusions: In rats, a nonfunctional renal papilla does not attenuate enhanced RIHP, UNOxV and diuretic responses to SVE, though decreases ~35% the late natriuretic response to SVE. Apparently, RMBF is a necessary but not sufficient factor for RIHP response to SVE.Grant Funding Source: Supported by IPL's financial resources