SUMMARY The histochemical utilization of 3α-, 3β-, 6β-, 11α-, 11β-, 12α-, 16α-, 16β-, 17α-, 17β-, 20α-, 21- and 24-hydroxysteroids by three normal adult human adrenal glands, two human foetal adrenal glands, three adrenals from patients with Cushing's syndrome and one adrenal adenoma are described. The normal adult human adrenal showed high 16β-hydroxysteroid dehydrogenase activity in the zona glomerulosa. Activity restricted to the outer part of the zona fasciculata was recorded with 3α-, 3β-, 6β-, 11β-, 16α-, 16β-, and 17β-hydroxysteroids. The zona reticularis utilized 3α-, 3β-, 11β-, 16β- and 17β-hydroxysteroids less well than the zona fasciculata. The adrenals of Cushing's syndrome showed activity only for 3β- and 16β-hydroxysteroid dehydrogenases; this activity was noted in all three zones. The activity pattern of the adrenal adenoma resembled that of the normal adult human adrenal except that greater activity for 16α-hydroxysteroid dehydrogenase was noted. The foetal part of the human foetal cortex was extremely active, showing 3α-, 3β-, 6β-, 11β-, 12α-, 16α-, 16β-, 17β-, 20β- and 21-hydroxysteroid dehydrogenase activity. The definitive cortex behaved similarly to the adult gland and possessed 3α-, 3β-, 11β-, 16β- and 17β-hydroxysteroid dehydrogenases; some evidence of zoning of the definitive cortex was seen with the 16β-hydroxysteroid. The relevance of these findings in the light of current knowledge of adrenal zonation is discussed.