The electron microscopical picture of the adrenal cortex in intact, adult, male, white mice is characterized by the following main features and their zonal variations. The adrenal gland is invested by a capsule composed of fibrils arranged in bundles and of basement-membrane-like capsular membranes interwoven between 3 to 4 layers of radially flattened cells. The adrenocortical capillaries are provided with an endothelial wall only 400thick along most of the luminal perimeter, and in this wall there are cytoplasmic discontinuities with a width of 400which are bridged by a simple membrane 50thick. Vesicles having a diameter of 500are the most characteristic feature in the cytoplasm of the endothelial cells. Throughout the adrenal cortex a space separates every capillary endothelium from neighbouring epithelial structures. This space is continuous with the intercommunicating system of extracellular spaces around the epithelial columns. Hence the entire adrenal cortex is pervaded by an intricate network of spaces which actually are branches of a single integral space. This is here as a whole called the periendothelial space. The periendothelial space generally contains two basement membranes—one epithelial and one endothelial or two epithelial. Pericapillary cells are found in the periendothelial space between basement membranes. Their nuclei and perinuclear cytoplasm is encountered near a capillary and the rest of the cytoplasm forms long processes extending into the periendothelial space, the cell as a whole apparently being especially adapted to conform with the configuration of this space. In addition the periendothelial space contains up to 0.4 μ long and 650thick microvilli projecting from the epithelial cells. Here four adrenocortical zones have been distinguished which, proceeding from the capsule to the medulla, are called the glomerular zone, the outer fascicular zone, the inner fascicular zone and the reticular zone. Mitochondria are plentiful in the epithelial cells of all cortical zones but their shape, outer membrane and inner structure exhibit zonal differences. The mitochondria differ significantly in breadth from one zone to another. The mitochondrial outer membrane, for the most part three-layered, may be simple along occasional portions of the periphery. Whilst the glomerular zone exclusively has mitochondria of tubulosaccular type, the mitochondrial inner structure in the deeper zones may be either tubulosaccular or membranous; and if membranous, predominantly rectimembranous in the outer fascicular zone and mainly cyclomembranous in the inner fascicular zone. Lipid droplets occur in the epithelial cells of all cortical zones. They are of round or oval shape in the two peripheral zones and irregular in the two deeper zones. Lipid droplets are usually intensely osmiophilic throughout in the glomerular, inner fascicular and reticular zones, whereas in the outer fascicular zone the osmiophilic matter in the lipid droplets tends to be concentrated into lumps or grains in the central portions of the droplet and into a marginal zone. Some droplets are entirely lacking in osmiophilic matter so they are instead called lipid vacuoles. Globules, round formations 0.33 μ in diameter outlined by a smooth and even three-layered surface membrane, are encountered in all cortical zones. Globules have a heterogeneous inner structure composed partly of regions with dense granules, partly of patches of homogeneously dark matter. The number of globules in a cell increases with increasing distance from the adrenal periphery. Cytoplasmic vacuoles and cytoplasmic vesicles occur in all cortical zones but are most numerous in epithelial cells from the two deeper zones. The cytoplasm of epithelial cells contains dense minute granules with a diameter of 150 . They are most numerous in glomerular epithelial cells and become less frequent with increasing depth into the cortex. In the reticular zone pigment bodies are seen which often exhibit a structure composed of arcuated osmiophilic stripes around light areas with dense granules along the boundary between the two former components. After parenteral administration of 1 mg of hydrocortisone acetate daily for 7 days, the adrenal cortex in similar mice exhibited ultrastructural changes varying in degree from animal to animal and from epithelial cell to epithelial cell but tending to be most pronounced in the deeper portions of the cortex. The main characteristic of the altered epithelial cells was the appearance of a great number of large lipid vacuoles among which a few mitochondria scarcely could be distinguished. Moreover, the number of pigment bodies was greater and pigment-like masses had appeared, particularly in the cells in the deep cortical zones. In a fluorescence microscopic control study it was verified that yellow fluorescing granules occur in the reticular zone of the cortex in intact mice and also that the number of such yellow fluorescing granules was significantly higher in mice which had received hydrocortisone parenterally as described above.