Using deoxycorticosterone acetate (DOCA)–salt rats, we tested the hypothesis that increased plasma NaCl concentration supports sympathetic activity and blood pressure (BP) during salt-sensitive hypertension. One day before experimentation, femoral catheters and an electrode for measurement of lumbar sympathetic nerve activity (LSNA) probe were surgically positioned in DOCA-salt and Sham-salt rats. DOCA-salt rats exhibited increased (P<0.05) BP and NaCl concentration (BP, 163±8 mm Hg; NaCl, 260.8±3.3 mEq/L [DOCA-salt]: BP, 106.3±4.2 mm Hg; NaCl, 254.3±1.7 mEq/L [Sham-salt]). After V₁ vasopressin blockade (Manning compound, 5 μg IV), infusion (0.12 mL/min) of 5% dextrose in water decreased NaCl concentrations, BP (−28±7 mm Hg), and LSNA (−39±5%) in DOCA-salt but not Sham-salt rats. To explain how such small (≈2%) increases in plasma NaCl could underlie the hypertension, we hypothesized that DOCA augments the pressor and sympathoexcitatory actions of NaCl. To address this hypothesis, animals with equally elevated NaCl but no DOCA (Sham-1.7% salt) and animals with increased DOCA but normal NaCl levels (DOCA-water) were prepared and administered the infusion of 5% dextrose in water. BP and LSNA were not altered in DOCA-water rats. In the Sham-1.7% salt rats, BP fell (P<0.05), but not LSNA, and the responses were significantly smaller than that observed in the DOCA-salt animals. Collectively, these data suggest that increased NaCl levels contribute to sympathoexcitation and hypertension in DOCA-salt rats because of amplification of the NaCl signal by DOCA.