It has been demonstrated, using doses of cortisone of 5 to 20 mg. per day, that pregnant rats exhibit a marked resistance to the biochemical effects of cortisone administration. This resistance was evident with respect to changes in alanine-glutamic transaminase activity, blood amino nitrogen and sugar levels and nitrogen balance data. There was no apparent resistance to the increase in liver weightproduced by the hormone. Removal of the fetus alone did not affect this resistance whereas removal of both the fetus and placenta abolished it. It has been concluded that the placenta is essential for the maintenance of the resistance to the effectsof cortisone seen in the pregnant rat. The possible mechanisms of this resistance are considered.