The purpose of this investigation was to measure quantitatively nuclear volumes in outer fasciculata cells in adrenal glands of rats subjected to chronic stimulation of steroidogenesis by ACTH, or to chronic inhibition of functional activity by hypophysectomy or by injection of the steroidogenic inhibitos, U-8113 (p-aminophenyl butanone) and SU-4885 (metopirone). Nuclear volumes, after a recovery period from those effects, were also measured. Chronic daily administrations of ACTH for 7, 14, and 30 days led to a progressive, statistically significant increase in nuclear volumes of fasciculata cells. These changes were found to have been reversed 14 days after discontinuation of hormone treatment. Hypophysectomy resulted in a significant decrease in nuclear volumes. The steroidogenic inhibitors SU-4885 and U-8113 had a biphasic effect on the nuclear volumes with an early decrease and subsequent increase to normal values. Since a decrease in nuclear volumes in the adrenal glands of inhibitor-treated subjects occurred in the presence of cellular hypertrophy and a significant increase in adrenal weights, it is concluded that changes in nuclear volumes can be positively correlated with the secretory activity of the cell rather than with the sizes of cells or glands.