Hypertension is a common finding in patients with Cushing's syndrome (CS), but the cause is unknown. One possibility is excess production of nonaldosterone mineralocorticoids, such as 19-nor-deoxycorticosterone (19-Nor-DOC). To evaluate this possibility we measured urinary 19-Nor-DOC glucuronide in normal subjects (n = 14) and patients with essential hypertension (n = 10), pituitary-dependent CS (n = 8), and adrenal tumors producing CS (n = 6). The subjects were admitted to a metabolic unit where 24-h urine samples were collected while they ate an isocaloric diet (128 meq Na+ 80 meq K+/day). 19-Nor-DOC glucuronide was purified by extraction and chromatography and measured by RIA. Urinary 19-Nor-DOC glucuronide excretion was significantly higher in patients with both pituitary CS and adrenal CS compared to that in normal subjects, while the values in the two CS groups were similar. The patients with essential hypertension also had elevated urinary 19-Nor-DOC glucuronide excretion, although the values were lower than those in either CS group. These results demonstrate that a nonaldosterone mineralocorticoid, 19-Nor-DOC, is produced in excess in patients with either pituitary or adrenal CS and, thus, suggest a possible role for 19-Nor-DOC in the pathogenesis of some hypertensive disorders.