BACKGROUND Glucocorticoids play a key role in blood pressure (BP) control and are associated with hypertension in patients with Cushing's syndrome. A number of reports indicate that cortisol (F) may be involved in etiology of essential hypertension (EH). F can bind to the mineralocorticoid receptor, triggering both sodium and water reabsorption in kidney, increase BP and cause renin suppression. OBJECTIVE To evaluate urinary free cortisol (UFF) excretion as a potential intermediate phenotype of essential hypertension and correlate F level with plasma renin activity (PRA) and serum aldosterone (SA). METHODS We recruited 132 EH patients and 16 normotensive healthy controls. Blood samples and 24 hours urine were collected for PRA, SA and UFF analysis. Differences in UFF excretion between sexes were normalized by urinary creatinine (Creat) excretion. The upper limit of UFF/Creat was determined in normotensives considering the mean value plus 2 standard deviations. According to this value, subjects were classified as having high or normal UFF. RESULTS In EH patients and in normotensives, the UFF/Creat was 36.9 +/- 17.0 microg/gr and 30.9 +/- 8.8 microg/gr, respectively. The upper limit was set at 48.5 microg/gr. A high UFF/Creat was found in 20/132 EH (15%) patients and 0/16 normotensive subjects. EH patients with high UFF showed lower PRA levels than patients with normal cortisol levels (0.78 +/- 0.47 vs. 1.13 +/- 0.66 ng/ml x h, respectively, p=0.027) and lower SA values (4.52 +/- 1.65 vs 6.34 +/- 3.37 ng/dl, respectively, p=0.018). There was a negative correlation between UFF and PRA (r=-0.176, p=0.044) and between UFF and SA (r=-0.183, p=0.036). CONCLUSIONS We have identified a subgroup of EH patients with increased UFF excretion. Patients with the highest UFF showed lower renin and aldosterone levels. These data suggest a potential influence of cortisol in the genesis of hypertension.