Abnormalities in erythrocyte Li-Na countertransport have been reported in hypertensive subjects, and the available evidence favors familial aggregation and striking heritability of this marker. It is uncertain, however, whether the abnormalities are associated with hypertension per se or whether they may be concentrated in a particular subset of hypertensive subjects. In the present study, maximal rates of Li-Na countertransport were measured in red blood cells of 82 white subjects, including 37 normotensive subjects and 45 normal- or high-renin hypertensive subjects previously classified as non-modulators (n = 21) or modulators (n = 24). Mean countertransport activity was significantly higher in non-modulators compared with normally modulating hypertensive or normotensive subjects (0.475 +/- 0.044 vs. 0.309 +/- 0.028 or 0.249 +/- 0.012 mmol/l cell x hr, respectively, p less than 0.001). Modulators did not differ significantly from normotensive subjects with regard to mean countertransport activity. Red blood cell sodium pump and Na-K-Cl cotransport were not significantly different in modulating and non-modulating hypertensive subjects. These relations remained unchanged after adjusting for age, body weight, and plasma cholesterol levels by analysis of covariance. A countertransport value exceeding 0.50 mmol/l cell x hr occurred in 40% of the non-modulators but in only one of the other subjects. In contrast , while one half of the modulators and normotensive subjects had a countertransport value less than 0.235 mmol/l cell x hr, none of the non-modulators did. Thus, elevated countertransport appears to aggregate in the non-modulating subset of essential hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)