Differences in cellular Na+ and K+ regulation may relate to the pathogenesis of essential hypertension and the predisposition of blacks to this disease. To explore these tenets, we examined several aspects of cellular Na+ homeostasis in serially passed, cultured skin fibroblasts from 30 subjects (15 hypertensive blacks and whites and normotensive subjects matched for sex, age, and race.) Fibroblasts from blacks demonstrated higher cellular Na+ turnover rates than did those from whites. This difference was expressed by accelerated Na+-K+ pump activity (ouabain-sensitive Na+ washout rate, 3.46 ± 0.216 for blacks vs 1.84 ± 0.283 mEq/IVmin for whites; p=0.0006) and a higher rate of cellular accumulation of Na+ in the presence of ouabain (0.964 ± 0.0743 vs 0.562 ± 0.0440 mEq/IVmln f°r blacks and whites, respectively; p=0.0045). Associated with these findings, fibroblasts from blacks had higher cellular Na+ concentration than did those from whites (9.78 ± 0.512 vs 7.50 ± 0.400 raEq/L; p=0.0170, as measured by atomic absorption, and 7.84 ± 0.470 vs 5.03 ± 0.980 mEq/L; p=0.0141, as derived from the equilibrium distribution ratio of22Na+). It is concluded that blacks differ from whites with respect to cellular Na+ turnover rate, which is evidenced by an increased Na+ influx and accelerated Na+-K+ pump activity in their fibroblasts. Our findings support the tenet that innate racial differences in cellular Na+ regulation may underlie the predisposition of blacks to hypertension.