The synthetic steroid nivazol lacks three of the substituents considered to be important for glucocorticoid activity, i.e. the 3-keto, the 11-hydroxy, and the 20-keto groups. Nevertheless, in the rat, nivazol has the activity profile of a glucocorticoid. Nivazol elicits numerous glucocorticoid activities in the rodent, but only the inhibition of the hypothalamic-pituitary-adrenal axis was observed in the primate. Nivazol has been investigated with respect to the treatment of Cushing's disease. In a patient with Nelson's syndrome nivazol was clearly highly effective in decreasing plasma ACTH concentrations and pigmentation. Its mechanism of action is similar to that of hydrocortisone. Both steroids directly inhibit in vitro ACTH secretion from corticotroph tumour cells removed from patients with Nelson's syndrome and block stimulation of ACTH release by ovine corticotrophin releasing factor and arginine vasopressin.