18-Hydroxy-ll-deoxycorticosterone (18-OH-DOC) was isolated from human adrenal vein blood in concentrations of the same magnitude as is aldosterone, and its structure was proved by a variety of methods including mass spectral analysis. Angiotensin infusions failed to evoke a rise in 18-OH-DOC secretion, whereas ACTH increased 18-OH-DOC secretion up to 20-fold. The secretion rate of 18-OH-DOC determined by isotope dilution in healthy subjects was similar to the range of aldosterone secretion. Excretion of the ring A reduced glucuronide metabolite, 18-hydroxy-tetrahydro-deoxycorticosterone (18-OH-TH DOC), in urine proved to be a valid index of secretion of 18-OH-DOC. 18-OH-DOC secretion was estimated in a variety of hypertensive disorders and found to be significantly elevated in a few (3 of 12) patients with essential hypertension, suppressed plasma renin activity, low or normal aldosterone secretion, and who had significant reduction in blood pressure with spironolactone. A single patient became normotensive on prolonged dexamethasone suppression of ACTH and 18-OH-DOC secretion. The possibility that 18-OH-DOC is a precursor of some more oxygenated and, perhaps, more active mineralocorticoid is suggested.