Orexins A and B are two hypothalamic peptides, that play a role in the central control of food intake. Orexins act via two subtypes of receptors: OX1R which is selective for orexin A, and OX2R which binds both orexins. Reverse transcription-polymerase chain reaction demonstrated the expression of both OX1R and OX2R gene in the adrenal cortex of adult female rats. The prolonged systemic administration of orexins A and B (20 ng/kg x day, for 7 days) affected neither adrenal weight and the morphology of adrenocortical zones (as evaluated by morphometric techniques) nor ACTH plasma concentration in rats. In contrast, the treatment with both orexins increased plasma concentration of both aldosterone and corticosterone. Taken together, these findings indicate that orexins exert a marked direct chronic secretagogue action on adrenocortical cells, acting through both OX1R and OX2R.