Slices of liver, spleen, and kidney incubated in Krebs soln. for 3 hrs. with added cortisone caused approx. a 70% loss of cortisone activity. Blood serum and brain or muscle slices were inactive. Tissue homogenates were much less effective than slices. Incubation of the tissue-cortisone mixture with the enzyme, glueuronidase; did not alter the exptl. findings. There was no detectable difference in the capacity of tissues of stressed or adrenalectomized animals, as compared to tissues from normal rats, to inactivate cortisone. The inactivation mechanism could not be altered by the pre-admn. of progesterone, pregnenolone, testosterone, desoxycorticosterone or cortisone.