Na(+) loading without Cl(-) fails to increase blood pressure in the DOCA model. We compared the changes in the total body (TB) effective Na(+), K(+), Cl(-), and water (TBW) content as well as in intracellular (ICV) or extracellular (ECV) volume in rats receiving DOCA-NaCl, DOCA-NaHCO(3), or DOCA-KHCO(3). We divided 42 male rats into 5 groups. Group 1 was untreated, group 2 received 1% NaCl, and groups 3, 4, and 5 were treated with DOCA and received 1% NaCl, 1.44% NaHCO(3), or 1.7% KHCO(3) to drink. We measured mean arterial blood pressure (MAP) directly after 3 wk. Tissue electrolyte and water content was measured by chemical analysis. Compared with control rats, DOCA-NaCl increased MAP while DOCA-NaHCO(3) and DOCA-KHCO(3) did not. DOCA-NaCl increased TBNa(+) 26% but only moderately increased TBW. DOCA-NaHCO(3) led to similar TBNa(+) excess, while TBW and ICV, but not ECV, were increased more than in DOCA-NaCl rats. DOCA-KHCO(3) did not affect TBNa(+) or volume. At a given TB(Na(+)+K(+)) and TBW, MAP in DOCA-NaCl rats was higher than in control, DOCA-NaHCO(3), and DOCA-KHCO(3) rats, indicating that hypertension in DOCA-NaCl rats was not dependent on TB(Na(+)+K(+)) and water mass balance. Skin volume retention was hypertonic compared with serum and paralleled hypertension in DOCA-NaCl rats. These rats had higher TB(Na(+)+K(+))-to-TBW ratio in accumulated fluid than DOCA-NaHCO(3) rats. DOCA-NaCl rats also had increased intracellular Cl(-) concentrations in skeletal muscle. We conclude that excessive cellular electrolyte redistribution and/or intracellular Na(+) or Cl(-) accumulation may play an important role in the pathogenesis of salt-sensitive hypertension.