The metabolism of 11-oxy 17-ketosteroids was studied by administration of labeled 11β-hydroxy and 11-keto androst-4-ene-3,17-dione (110HΔ and 11KΔ) and hydrocortisone to 8 normal subjects and to 4 patients with adrenal or gonadal disease. The urinary metabolites of 11OHΔ and 11UKΔ had similar ratios of 5α/5β reduction products, ranging from 2.5 to 8.6 in both normal and abnormal subjects. With simultaneous administration of hydrocortisone and 11OHΔ, it was possible, given certain assumptions, to estimate the production of the latter compound peripherally from hydrocortisone as well as its de novo secretion by the adrenal. In one normal subject, in one patient with ovarian dysgenesis, and in one with adrenal hyperplasia, there was no detectable peripheral formation of 11OHΔ or 11KΔ; the secretion rate of 11OHΔ was estimated at 3.8 and 5.3 mg/day in the first 2 instances. In another case of Cushing's syndrome 5.9 mg 11OHΔ/day was produced, 78% by de novo secretion; in a patient with a functioning adrenal tumor, the 11OHΔ secretion was estimated to be between 5.9 and 8.7 mg/day. In these instances, it could be estimated, further, that about 20% of the urinary C19O3 steroids derived from hydrocortisone originated via the formation of 11OHΔ, while 80% originated from side-chain cleavage after hydrocortisone had been reduced in ring A.