Atrophy of the adrenal gland induced by thyroparathyroidectomy (TPX) is attributable primarily to narrowing of the zona fasciculata. But absolute volumes of the adrenal gland and zona fasciculata, not the zona glomerulosa and zona reticularis, were decreased significantly 7 weeks after TPX. Changes consistent with atrophy were also seen in the zona fasciculata by electron microscopy. A slight decrease in volume of cytoplasm in cells of the zona fasciculata was evident 2 weeks after TPX as shown by quantitative stereological techniques. Seven weeks after TPX, there was a significant decrease in average cytoplasmic volume as well as mitochondrial volume and surface density of mitochondrial membranes. A decrease in total volume of the zona fasciculata, as well as volume per cell of mitochondria, correlates directly with decreased production of corticosterone in response to stress in TPX rats. Parathyroidectomy (PX) had no effect on the volume of the adrenal gland, on the volume of the individual cortical zones, or on the volume per cell of cytoplasm or mitochondria; these observations indicate that changes in TPX rats are due primarily to ablation of the thyroid gland.