Hypercholesterolemia and hypertension are frequently associated risk factors for cardiovascular diseases. The interactions between hypercholesterolemia and the regulatory mechanisms of blood pressure are poorly understood. In this study we investigated the effects of hypercholesterolemia on salt metabolism and its hormonal control mechanisms in spontaneously hypertensive rats (SHR). Six-week-old SHR were randomly assigned to either a high (1%) cholesterol diet or a matched regular diet for 6 weeks, followed by a 2-week dietary washout. A group of normotensive Wistar-Kyoto rats received the high cholesterol diet and was used as a control. Plasma cholesterol increased significantly (P < 0.001) in both cholesterol-fed SHR and Wistar-Kyoto rats. Blood pressure was unaffected by 6 weeks of a high cholesterol diet. Hypercholesterolemia caused a significant increase in aldosterone (by analysis of variance: F = 8.40; P < 0.01) associated with a significant decrease in corticosterone (F = 4.64; P < 0.05) in the SHR, but not in the normotensive rats. In addition, in the cholesterol-fed SHR, urinary sodium excretion was reduced (P < 0.01), and the urinary potassium/sodium ratio was increased (P < 0.01) compared to those in the remaining groups of rats. The hormonal and urinary differences between the hypertensive subgroups were not detectable after withdrawal of cholesterol. These results demonstrate that diet-induced hypercholesterolemia specifically promotes reversible mineralocorticoid accumulation and sodium retention in SHR.