Findings from hypertension research indicate that dietary sodium chloride (NaCl), Na+, and Cl- independently influence blood pressure, electrolyte metabolism, and hormone secretion. In this context, we examined the effects of NaCl, Na+, and Cl- depletion, respectively, on the development of saline preference (salt appetite) in rats. Male Wistar rats were given a normal diet (1% NaCl) for 15 days and tested for salt appetite using a two-bottle choice test, one bottle containing water and the other 0.3 M saline. The animals were then divided into three groups (n = 11/group): one group received low NaCl, another received a Na(+)-deficient, normal-Cl-diet (low Na+), and a third received a Cl(-)-deficient, normal-Na+ diet (low Cl-). Salt appetite was again tested after 19 days on these diets. Both NaCl and Na+ depletion stimulated saline intake (P less than 0.01), whereas salt appetite did not change in the low-Cl- group. Water intake was not influenced by the regimens. In addition, no alterations were noted for weight, systolic blood pressure, plasma Na+ concentration, or blood pH. Dietary Cl-depletion, however, significantly reduced plasma Cl- concentration (P less than 0.05), and reduced plasma potassium in relation to rats depleted in Na+ (P less than 0.05). Plasma renin activity and urinary aldosterone were elevated in low-NaCl and Na(+)-depleted rats relative to the Cl(-)-depleted group (P less than 0.05). These results suggest that salt appetite is increased by dietary Na+ deficiency but not by Cl- deficiency. Salt appetite may be controlled by central or peripheral systems specifically sensitive to Na+ or by hormonal changes characteristic of Na+ depletion, such as the activation of renin and aldosterone observed in the low-NaCl and low-Na+ groups.