The predisposition of black people to salt (NaCl)-sensitive essential hypertension may relate to racial differences in cellular Na+ metabolism. This tenet was investigated by examining the Na(+)-H+ antiport in serially passed skin fibroblasts from blacks and whites. Na(+)-dependent stimulation of the Na(+)-H+ antiport by cellular acidification resulted in a greater maximal velocity (Vmax) (mean +/- SEM) of this transport system in quiescent fibroblasts from blacks than fibroblasts from whites; the Vmax for recovery from cellular pH (pHi) of 6.6 was 5.84 +/- 0.50 versus 4.39 +/- 0.34 mmol H+/l X 20 seconds for blacks and whites, respectively (p less than 0.05). Although the Na+ concentration producing 50% stimulation of the Na(+)-H+ antiport for blacks (35.1 +/- 5.7 mM) was greater than for whites (24.1 +/- 3.5 mM), this difference was not statistically significant. No racial differences were observed in the Hill coefficient (n, 1.35 +/- 0.21 for blacks and 1.46 +/- 0.28 for whites). Compared with whites, cells from blacks exhibited a greater response to cytoplasmic acidification over the range of pHi values 6.20-6.60, as exhibited by an augmented rate of recovery in the pHi. These differences were not due to different basal pHi values or cellular buffering capacities, which were similar for blacks and whites. Na(+)-H+ antiport activity was not correlated with family history of hypertension. Increased activity of the Na(+)-H+ antiport in fibroblasts from blacks was confirmed without cellular acidification by stimulating quiescent cells with 10% human serum. This study demonstrates innate racial differences in cellular membrane Na(+)-H+ antiport activity.