The present study was designed to investigate the role of abnormalities in red blood cell sodium-potassium-chloride (Na-K-Cl) cotransport and Na+ pump as predictors of the pressor response to chronic oral Na+ loading in young whites and blacks. Subjects were healthy adults from 18 to 23 years of age and included normotensive whites (n= 24) and normotensive blacks (n= 35). Red blood cell transport studies were performed before Na+ loading. The Na+ load consisted of 10 g NaCl daily added to the usual diet A sodium-sensitive response was denned as an increase of 5 mm Hg or more in mean arterial pressure after the Na+ load; a sodium-insensitive response was a less than 5 mm Hg increase in mean arterial pressure. A sodium-sensitive response occurred in 16% of whites and 57% of blacks. Black subjects have a significantly lower (p< 0.005) maximal rate of furosemide-sensitive Na+ efflux and a higher Kmfor cellular Na+ (p< 0.05) to activate Na-K-Cl cotransport than white subjects. Normotensive blacks with sodium-sensitive blood pressure response had a higher Km(14.4±6 mmol/1 cell,n= 17, mean±SD) to activate the cotransport than sodium-insensitive blacks (9.9±3.7 mmol/1 cell,n= 13,p< 0.001). Normotensive whites had a significantly lower red blood cell Na+ content (p< 0.05) and a higher maximal rate of cotransport (p< 0.005) than young normotensive blacks. The four young whites with a sodium-sensitive blood pressure response had a significantly lower maximal rate of the cotransport than the sodium-insensitive subjects. The maximal rate of ouabain-sensitive Na+ efflux was similar in blacks and whites and in sodium-sensitive and sodium-insensitive subjects, but it displayed significant sex differences in all groups. These results indicate that a high Kmof the Na-K-Cl cotransport is a predictor of a sodium-sensitive blood pressure in normotensive young blacks.