To study the contribution of adrenomedullin in the adrenal medulla in the stress response, we measured plasma and adrenal levels of adrenomedullin in sham-operated (intact) rats and in rats without adrenal medulla, with or without exposure to ether vapor for 15 min. Adrenomedullin levels decreased drastically after demedullation. Effect stress resulted in increased adrenomedullin levels in both adrenal and plasma in sham-operated rats, but not in demedullated rats. The responses of plasma adrenocorticotropin to stress were similar, but the elevations in plasma corticosterone levels were significantly less in demedullated rats. In the sham-operated rat, preproadrenomedullin mRNA levels were increased after stress, and this effect was not blocked by pretreatment with hexamethonium. We conclude that stress increases adrenomedullin synthesis and secretion from the adrenal medulla through a hexamethonium-insensitive mechanism, and that adrenomedullin release from the adrenal medulla may play a role in cortical steroidogenesis.