11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) modulates the access of corticosteroids to their receptors and is important in blood pressure control. The excretion of renal 11 beta-HSD (ie, NAD+-dependent isoform) is thought to protect renal mineralocorticoid receptors from cortisol. To examine whether endogenous renal 11 beta-HSD inhibitory factor(s) may be involved in the pathophysiology of hypertension, we studied the urinary excretion of such inhibitors in 30 patients with low-renin essential hypertension and 20 normotensive control subjects. The effect of sodium restriction on the urinary excretion of the inhibitors was also evaluated in six normotensive control subjects. Urine was extracted with Sep-Pak cartridges and high-performance liquid chromatography. Endogenous renal 11 beta-HSD inhibitors were measured by the inhibition of 11 beta-HSD bioactivity in microsomes from the human kidney.