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.