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To study the activity of the Na+-dependent CI-–HCO3- anion exchanger in erythrocytes of patients with essential hypertension.The study was performed in cells from 48 untreated essential hypertensive patients and 30 normotensive controls with similar age- and sex- distribution.The activity of the Na+-dependent anion exchanger was determined by measuring the 4,4´-diisothiocyanostilbene-2,2´-disulfonate (DIDS) sensitive Li+ influx in fresh cells incubated into a medium containing Li2CO3.The DIDS-sensitive Li+ influx was higher in hypertensives than controls. With the 100% confidence (upper) limit of the normotensive population as a cut-off point, a subgroup of 11 hypertensives had an abnormally high activity of the Na+ -dependent CI--HCO3- anion exchanger. Compared with patients with normal exchanger activity, patients with increased exchanger activity were characterized by the following: higher frequency of family history of hypertension; lower serum high-density lipoprotein cholesterol levels and higher plasma aldosterone concentrations. After multiple regression analysis, the DIDS-sensitive Li+ influx was inversely correlated with high-density lipoprotein cholesterol levels.These results show the presence of a new abnormality of erythrocyte Na+ transport in essential hypertension — increased activity of the Na+-dependent Cl--HCO3- anion exchanger. In addition, our findings suggest that from the clinical point of view, patients with this transport abnormality represent a particular subset of essential hypertensives.