Cytosol binding of [3H]corticosterone and [3H]dexamethasone was measured in various brain areas and the pituitary of perfused rats 12 h and 72 h, respectively, after adrenalectomy (ADX). A considerable regional heterogeneity was found 12 h post ADX representing differences of the normal cytosol binding capacities between various areas. When the second phase of the adrenalectomy-induced increase in binding capacity was allowed to develop (72 h post ADX), the cytosol binding of all regions increased to various extents. The highest percentage increases were found in those areas with the highest glucocorticoid binding capacity, namely the hippocampus and the septum. The ontogeny of the cytosol glucocorticoid binding macromolecules was investigated in the hippocampus, hypothalamus and pituitary using [3H]corticosterone and [3H]dexamethasone. The concentration of corticosterone binding sites is lowest in all three areas around day one and then increases by a factor of 2-3 reaching adult levels around day 32. For [3H]dexamethasone a similar pattern was observed in the hippocampus and hypothalamus. In the pituitary, however, the concentration of binding sites was slightly higher at day 1 than at any later developmental stage. Interruption of the fimbria in 3-day-old rats did not affect the development of the binding sites in the hippocampus. In an attempt to interfere with the normal glucocorticoid binding of the hippocampus as well as with the postadrenalectomy increase of the cytosol binding sites, bilateral transection of the fimbria was performed either 3 days or 80 days before ADX. In neither case did fimbria transection prevent the increase of the binding sites. The intrinsic (12 h post ADX) cytosol binding capacity of the hippocampus was also not affected by this lesion.