We studied body weight (BW), serum Na, osmolality (Osm), urine sodium excretion (UNaV) and sodium balance (NaBal) responses to a 24-hr 460 mEq sodium load in 53 subjects (32 hypertensive HTN, 21 normotensive NTN) classified as salt-resistant (SR) or salt-sensitive (SS) with an in-patient protocol. Cutoff for SS was a fall in mean daytime systolic BP (Spacelabs 90207) of ≥10 mmHg from high- to low-salt (10 mEq Na diet plus furosemide 40 mg x 3). UNaV (SR 362±22 vs SS 353±21 mEq/day) and NaBal (SR 98±22 vs SS 107±21 mEq/day) did not differ between groups. In contrast, SR had non-significant BW loss (-0.2±0.2 kg) whereas SS gained BW (0.8±0.2, p<0.001), suggesting different water balances; supported by a differential trend of changes in Na between SR (0.6±0.4 mEq) and SS (-0.3±0.5, p~0.07) and lack of change of Osm in SR (0.04±0.86 mOsm) versus a significant reduction in SS (-1.70±0.87, p<0.03). These observations were similar in HTN and NTN. We also measured hemodynamics (echocardiogram) in NTN during the high- and low-salt days. On low-salt, cardiac output (CO, 3.7±0.2 vs 4.0±0.5 L/min), mean arterial pressure (MAP, 85±2 vs 83±3 mmHg), and total peripheral resistance (TPR, 1896±92 vs 1767±163 dyn*cm-5*sec-1), were not different between SR and SS. On high-salt, SR significantly reduced TPR (-347±84 dyn*cm-5*sec-1; p<0.001) and maintained MAP (Δ -1±3 mmHg), whereas SS failed to vasodilate (ΔTPR +24.3±97.4, ns) and increased MAP (Δ 14±3; p<0.001). Atrial filling pressures increased equally with high-salt in both groups. In contrast, left ventricular (LV) filling pressures (E/e’ ratios) were higher in SS than in SR on both days (low-salt 9.0±0.9 vs 5.4±0.4, p<0.005, and high-salt 9.8±0.7 vs 7.7±0.3, p<0.03). Our data suggest that: 1. SR are able to store Na without concomitant water in an undefined compartment whereas this storage is impaired in SS; 2. water retention by SS is not intravascular because despite small effects on Na and Osm, their cardiac output response to salt was no greater than that in SR; and 3. inability of SS to vasodilate in response to salt and increased LV filling pressures regardless of salt-balance suggest a role for abnormal water metabolism in vascular smooth muscle and cardiomyocyte dysfunction, the former probably mediating pressure natriuresis.