Compared with age-matched men, women are resistant to the hypertensive effects of dietary NaCl; however, after menopause, the incidence of salt-sensitive hypertension is similar in women and men. We recently suggested that osmotically inactive Na[sup +] storage contributes to the development of salt-sensitive hypertension. The connective tissues, including those immediately below the skin that may serve as a reservoir for osmotically inactive Na[sup +] storage, are affected by menopause. We tested the hypothesis that ovariectomy (OVX) might reduce osmotically inactive Na[sup +] storage capacity in the body, particularly in the skin. Male, femalefertile, and female OVX Sprague-Dawley (SD) rats were fed a high (8%)- or low (0.1%)-NaCl diet. The groups received the diet for 4 or 8 wk. At the end of the experiment, subgroups received 0.9% saline infusion and urinary Na[sup +] and K[sup +] excretion was measured. Wet and dry weight (DW), water content in the body and skin, total body Na[sup +] (rTBNa[sup +]) and skin Na[sup +] (rSKNa[sup +]) content were measured relative to DW by desiccation and dry ashing. There were no gender differences in osmotically inactive Na[sup +] storage in SD rats. All SD rats accumulated Na[sup +] if fed 8% NaCl, but rTBNa[sup +] was lower in OVX rats than in fertile rats on a low (P < 0.001)- and a high (P < 0.05)-salt diet. OVX decreased rSKNa[sup +] (P < 0.01) in the rats. A high-salt diet led to Na[sup +] accumulation (ΔSKNa[sup +]) in the skin in all SD rats. Osmotically inactive skin Na[sup +] accumulation was ∼66% of ΔSKNa[sup +] in female and 82% in male-fertile rats, but there was no osmotically inactive Na[sup +] accumulation in OVX rats fed 8% NaCl. We conclude that skin is an osmotically inactive Na[sup +] reservoir that accumulates Na[sup +] when dietary NaCl is excessive. OVX leads to an acquired reduction of osmotically inactive Na[sup +] storage in SD rats that predisposes the rats to volume excess despite a reduced Na[sup +] content relative to body weight. [ABSTRACT FROM AUTHOR]