To assess the role of the GH/IGF-I axis in osmotic acclimation of the gilthead seabream Sparus aurata, juvenile specimens were acclimated to four environmental salinities: hyposmotic (5 ‰), isosmotic (12 ‰) and hyperosmotic (40 and 55 ‰). The full-length cDNAs for both pituitary adenylate cyclase-activating peptide (PACAP) and prepro-somatostatin-I (PSS-I), the precursor for mature somatostatin-I (SS-I), were cloned. Hypothalamic PACAP and PSS-I, hypophyseal growth hormone (GH) and prolactin (PRL), and hepatic insulin-like growth factor-I (IGF-I) mRNA expression levels were analyzed in the four rearing salinities tested. PACAP and IGF-I mRNA values increased significantly in response to both 5 and 55 ‰ salinities, showing a U-shaped curve relationship with the basal level in the 40 ‰ group. Hypothalamic PSS-I expression increased strongly in the 55 ‰ environment. GH mRNA levels did not change in any of the tested environmental salinities. PRL mRNA maximum levels were encountered in the 5 and 12 ‰ environments, but significantly down-regulated in the 40 ‰. Plasma cortisol levels significantly increased in the 40 ‰ environment. These results are discussed in relation to the well-known high adaptability of Sparus aurata to different environmental salinities and the role of the GH/IGF-I axis in this process.