The injn. of moderate amts. of estrogen into spayed 9 guinea pigs for a short period of time instigated hypertrophy of the adrenal cortex with an increase of relative adrenal wt. over that of the normal and castrated controls. Histologic study revealed that cortical hypertrophy was due to an increase in cell size in the fascicular and glomerulosar zones. Planimeter measurements were made of cross-sections through all glands. In the estrogen series, the reticular zone of degenerate cells was greatly increased in size, the fascicular zone was reduced, while the glomerculosar zone was increased as compared to the controls. The injn. of moderate amts. of progesterone for short periods of time caused an increase in relative adrenal wt. and an enlargement of the glomerculosar and reticularis zones. Histologically, the cortical cells showed an increment of size but otherwise resembled the controls. The life-maintaining properties of progesterone and the toxicity of estrogens are reflected in this study by the differential adrenal responses to injn. of the 2 sex hormones.