This investigation was designed to study specific glucocorticoid binding to cytoplasmic fraction and nuclei of thymus cells during rat development and to find out whether these data can be correlated to changes of RNA synthesizing activity of nuclei and cytoplasm. The dexamethasone binding capacity of cytoplasm rose rapidly in rats weighing up to 125 g and decreased significantly in animals weighing more than 160 g. Hormone binding to nuclei revealed similar but less pronounced changes. RNA synthesizing activity of nuclei measured by [3H]uridine incorporationin vitrodecreased from 57 ± 4.6 dpm/μg DNA in young to 23 ± 2.2 dpm/μg DNA in adult rats. RNA synthesizing activity of the cytoplasmic fraction fell 21.6% and that of purified polymerase IIIBfell 27.8% during development. Inhibition of RNA synthesis by dexamethasone appliedin vivoandin vitroshowed age-dependent differences. The RNA synthesizing capacity of nuclei was inhibited up to 39% in animals weighing 130 g and only 9% in aging rats. Similar changes were observed by incubation of intact thymocytes with and without hormone. The observed inhibitory effect of dexamethasone on RNA synthesis is well correlated to changes of cytoplasmic hormone receptor capacities during development.SpeculationIf the observations on developmental changes of hormone binding capacities and on age-dependent responses of thymus cells to glucocorticoid action can be applied in general, it is not the hormone itself, but the receptor concentration which seems to be the limiting factor for the cellular response to the hormone action. Therefore, efforts should be made to find ways to induce synthesis of these receptor proteins.