Abstract-Blacks have a greater tendency to retain Na than whites. The present study sought evidence for ethnic differences in parameters reflective of Na uptake by the Na,K,2Cl cotransporter in the thick ascending limb, namely, the urine concentration and urinary excretion of certain cations before and after furosemide administration (40 mg IV). Subjects were healthy (ages 18 to 36 years). During the preceding overnight period, urine volume was lower, and osmolality was higher in blacks than in whites, an ethnic difference that disappeared when water intake was restricted to infused normal saline (60 mL/h). Plasma vasopressin levels were higher in black males than in other sex/ethnic groups. Baseline urinary excretion rates of K, Ca, and Mg were significantly lower in blacks than in whites. After furosemide (0 to 1 hour), K and Ca excretion rates increased, but the proportionate ethnic difference decreased from 44% to 22% and from 22% to 10%, respectively, consistent with blacks having more basal Na,K,2Cl cotransporter activity to inhibit. During a later postfurosemide period (1 to 5 hours), urinary concentrations of Ca and Mg recovered more slowly in blacks, consistent with greater reuptake in the thick ascending limb. In summary, there were distinct ethnic differences in renal handling of Ca and Mg basally and in response to furosemide that were consistent with a more active Na,K,2Cl cotransporter in the thick ascending limb in blacks. An increase in vasopressin levels appeared to explain greater urine concentrations in black males but not black females. Key Words: Na,K,2Cl cotransporter Ⅲ aldosterone Ⅲ thick ascending limb Ⅲ osmolality Ⅲ ethnicity Ⅲ furosemide Ⅲ calcium B lacks, in comparison with whites, have lower levels of plasma renin activity (PRA) 1 and aldosterone 2 and are more likely to develop hypertension that is salt sensitive, 3 findings consistent with blacks having greater renal reabsorption of Na. Where in the nephron the greater uptake of Na occurs is unknown. We showed previously that amiloride, an inhibitor of the epithelial Na channel in distal nephron, significantly lowered blood pressure in whites when compared with blacks, consistent with less Na uptake by the epithelial Na channel in blacks, probably because of lower aldosterone levels. 4 Greater Na reabsorption in blacks appeared to take place at a more proximal nephron site. The thick ascending limb (TAL), a principal nephron region for reclamation of Na by way of the Na,K,2Cl cotransporter (NKCC2), 5 is a potential site for increased Na reabsorption. Although NKCC2 in TAL is more active in the salt-sensitive hypertensive Dahl rat, 6,7 NKCC2 has never been shown to cause hypertension in humans.Ethnic differences suggesting that TAL could be a site for more active Na uptake in blacks are described here: (1) Blacks have, on average, lower urine volumes and higher urine concentrations than whites. 8,9 Na taken up by NKCC2 in TAL is essential for maintaining the renal medullary osmotic gradient required for water reabsorption in the coll...