Compared with whites, blacks appear to retain additional sodium that suppresses secretion of renin and aldosterone. The epithelial sodium channel (ENaC) is an aldosterone-regulated site for sodium reabsorption. ENaC activity could be higher in blacks, contributing to sodium retention or, alternatively, lower because of reduced stimulation by aldosterone. To examine the level of ENaC activity in blacks relative to whites, blood pressure (BP) responses to amiloride (5 mg/d), an inhibitor of ENaC, were measured in 20 black and 25 white normotensive young people. After 1 week, systolic BP decreased by 3.0+/-9.2 (SD) and diastolic by 2.8+/-8.3 mm Hg in the whites, whereas systolic BP increased by 2.5+/-7.1 and diastolic by 3.8+/-8.0 mm Hg in the blacks; the racial difference in the BP response was significant for both systolic (P=0.034) and diastolic BP (P=0.010). As ENaC activity increases, renal secretion of potassium increases proportionately, and in a larger sample of subjects, the urinary potassium excretion rate was lower in the blacks (n=301) than in the whites (n=461): 3.2+/-0.1 versus 3.8+/-0.1 mmol/mmol creatinine (P=0.0001). The concentration of serum potassium was higher in the blacks (n=81) than in the whites (n=167): 4.36+/-0.05 versus 4.21+/-0.03 (P=0.012). In summary, a favorable BP response to amiloride in the whites as well as the evidence for greater retention of potassium in the blacks is consistent with blacks having less ENaC activity than whites. We suggest that increased sodium retention in blacks occurring at other nephron sites suppresses aldosterone secretion and in turn ENaC function.