The effect of short-term bilateral adrenalectomy (ADX) and corticosterone or aldosterone replacement was investigated on serotonin1 (5-HT1) receptor density in rat brain regions. One hour after ADX the 5-HT1 receptor density was increased in subiculum, molecular layer of the dentate gyrus, substantia nigra, and dorsal raphe nucleus as shown by in vitro autoradiography and computerized densitometric analyses of the film images. In subiculum, dentate gyrus, and dorsal raphe nucleus the 5-HT1 receptor density was restored (decreased) towards the level observed in sham-operated rats after administration of a low dose of corticosterone (CORT) at the time of ADX. CORT replacement decreased the 5-HT1 receptor number also in hippocampal pyramidal cell layer CA1, presubiculum, and other dentate gyrus subregions. The 5-HT1 receptor density was not affected by ADX or CORT replacement therapy in cerebral cortex, central grey, CA3, ventral hippocampus, and median raphe nucleus. Aldosterone administered under the same experimental conditions did not change the 5-HT1 receptor number in any of the hippocampus or raphe regions. The dose of CORT (30 µg/100 g body weight, s.c.) gave physiological plasma levels and maintained almost complete occupation of CORT receptors (mineralo-corticoid-like receptors) in hippocampus which was also the case in the sham-operated control animals. CORT replacement did not maintain occupancy of glucocorticoid receptors in hippocampus. When the binding of the selective glucocorticoid agonist, Η-RU 28362, was taken as 100% at 1 h after ADX, CORT replacement and sham ADX left 75 and 50% of these sites available respectively. It is concluded that the 5-HT1 receptor density in dorsal raphe and dorsal hippocampus regions is under selective control of CORT and that this 5-HT response seems to require occupation of the CORT(mineral-ocorticoid-like) receptor system in hippocampus neuron