SUMMARY: Possible mechanisms whereby the anabolic steroid methandienone lowers the urinary excretion of 17-KS and 17-OHCS have been studied in eight patients. Administration of the drug was associated with a delayed catabolism of infused cortisol and of endogenous cortisol, and a fall in cortisol production rate. In several patients, treatment was accompanied by a rise in certain serum enzyme levels and abnormal bromsulpthalein retention, but in others, these liver function tests were unaffected. Methandienone may thus inhibit the hepatic detoxification of cortisol without necessarily inducing changes in conventional liver function tests. The suppression of adrenocortical secretion was considered to be in part secondary to the effect of delayed cortisol catabolism, but evidence is also given suggesting a direct effect of the drug on the hypothalamus or pituitary, inhibiting the production or release of ACTH.