Since the acute inhibition of COR secretion in the healthy volunteers was paralleled by a simultaneous decrease of ACTH release, central mechanisms (for example, inhibition of hypothalamic CRH output) are suggested to be responsible for the inhibitory effects of mirtazapine on COR secretion. Our results are of particular interest in the light of the hypercortisolism observed in depressed patients and new pharmacological approaches such as CRH(1) receptor antagonists.