The interaction of three different Na+ transport systems (Na+-K+ pump, Na+-K+ cotransport and Na+-Li+ countertransport), with internal Na+ and the passive Na+ leaks, were measured in erythrocytes from 72 Spanish, essential hypertensive patients and 30 normotensive controls. According to the observed abnormalities in Na+ transport pathways, 93.1% of the patients were classified into the following subsets: 12 (16.7%) exhibited a decreased apparent affinity of Na+-K+ pump for internal Na+ (Pump "-" hypertensives); 20 (27.7%) showed a decreased apparent affinity of Na+-K+ cotransport for internal Na+ (Co "-" hypertensives); 27 (37.5%) showed an accelerated Na+-Li+ countertransport (Counter "+" hypertensives); and 5 (6.9%) exhibited an increased rate constant of passive Na+ leaks (Leak "+" hypertensives). Finally, 5 patients (6.9%) did not show any abnormality in their Na+ transport systems and 3 exhibited more than one. Moreover, distinctive clinical features were recognize in Co "-" and Counter "+" subsets. Blood pressure values were lower in the former and, conversely, Counter "+" hypertensives showed a higher prevalence of moderate or severe hypertension (65.5% vs. 32.6%; P = 0.0059) and higher values of stimulated plasma renin activity (1.63 +/- 0.52 vs. 0.81 +/- 0.15; P = 0.0443). Our results confirm the heterogeneity of Na+ transport abnormalities in essential hypertension and suggest that these subsets of hypertensives could represent clinical entities.