The present study investigates the role of melanotrope proopiomelanocortin-derived peptide in the interrenal stress response to different stressors in male gilthead sea bream, Sparus aurata. Plasma cortisol and acetyl salmon endorphin (acetyl s-EP), as well as pituitary acetyl s-EP contents, were measured during two stress paradigms: (a) long-term (1-month) confinement and crowding, and (b) short-term (60-min) confinement, crowding, and manipulation. In addition, naltrexone, a highly specific opioid receptor antagonist, was employed in some experimental groups to evaluate the adaptability of the opioid response to interrenal stress. In the long-term (1-month) confinement and crowding, higher plasma cortisol levels and acetyl s-EP concentrations than in the control group were found. However, although plasma cortisol levels significantly increased in both types of stress paradigm, a significant rise in plasma acetyl s-EP was observed only in the case of confinement plus crowding. These data seem to suggest a direct correlation of acetyl s-EP plasma levels exclusively in cases of specific stress, and support previous observations about the different nature of the pituitary-interrenal stress response in salmonids and in mammals. The results obtained in the short-term (60-min) experiments demonstrate the double activation of both the opioid and corticotrope systems when manipulation plus crowding was applied.