RECENT studies show that desaturation of the 1, 2 positions of hydro-cortisone and introduction of other substituents (2α-methyl- and 9αfluoro-groups) lead to increased biological activity (1, 2, 3, 4, 5, 6). On the basis of plasma steroid levels, it has been suggested that the prolonged biological half-life of steroid analogues is due to decrease in rate of metabolism by tissues (5, 7, 8, 9). Studies were initiated to determine whether elevated plasma levels and increased glycogen deposition activities of hydrocortisone derivatives are related to rate of inactivation in liver. In summary of much work in this area, it may be stated that C-20 and δ4-3 ketone reduction of hydrocortisone, as well as ketone reduction of a number of other steroids, occurs in a combined microsome-supernatant fraction of rat liver (10, 11, 12, 13). Hydrocortisone is reduced by rat liver enzyme systems to the corresponding dihydro and tetrahydro derivatives (10).