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To determine whether the membrane cholesterol distribution is associated with the increased activity of sodium–lithium countertransport in the erythrocytes of normocholesterolaemic and hypercholesterolaemic patients with untreated essential hypertension.Erythrocytes were prepared from venous blood samples obtained from normotensive subjects and hypertensive (normocholesterolaemic and hypercholesterolaemic) patients. The membrane cholesterol distribution between the inner and outer monolayers was measured by means of cholesterol oxidation to cholestenone after continuous cholesterol oxidase treatment. The sodium-lithium countertransport activity was determined by measurements of external sodium (150mmol/l)-stimulated lithium efflux. The statistical analysis was conducted by analysis of variance with Tukey's correction and correlations were performed by linear regression analysis using Pearson's correlation coefficient.The half-times for cholesterol oxidation were significantly higher in patients with untreated essential hypertension, either with (25.4±5.6 min) or without (21.7±2.9 min) concomitant hypercholesterolaemia, than in the controls (15.3±2.8 min). Sodium–lithium countertransport activities were also higher in the hypertensive patients (0.410±0.094 and 0.304±0.037 mmol/h per litre cell for the hypercholesterolaemic and normocholesterolaemic groups, respectively) than in the controls (0.262±0.081 mmol/h per litre cell). In single-regression analysis, the half-time for membrane cholesterol oxidation was positively correlated to the erythrocyte cation flux mediated by the sodium–lithium countertransport.It is hypothesized that the sodium–lithium countertransport activity might be influenced by membrane structural cholesterol domains.