Melengestrol, a steroid with progestational activity but with a structure that does not resemble that of cortisol, suppresses plasma cortisol in humans with a potency 1/40th that of dexamethasone. The 6alpha-methyl and 17alpha-acetoxy substituents and the 6,7 double bond of melengestrol acetate are known to slow the metabolism of similar steroids. Insertion of a 6alpha-methyl group markedly increases the glucocorticoid activity of 17alpha-OH-progesterone. The glucocorticoid activity of melengestrol is presumably attributable to the large dose administered in our study, its slow metabolism and limitations of the specificity of glucocorticoid tissue receptors.