Black porgy is a marine euryhaline species with a capacity to cope with demands in a wide range of salinities and thus is a perfect model-fish to study osmoregulatory responses to salinity-acclimated processes and their hormonal control. The present study was performed to understand the regulatory changes in hormone, hormone receptors and important osmoregulatory genes in pituitary, gill, intestine and kidney in response to acute salinity stress. Transcript levels were analyzed by quantitative real-time PCR following acute salinity challenge by direct transfer of seawater (SW) acclimatized fish to fresh water (FWBP) and vice versa (SWBP). SW acclimation significantly increased plasma osmolality and intestine Na+/K+-ATPase (NKA) activity while FW acclimation increased plasma cortisol and branchial NKA activity. Plasma osmolality and chloride concentration decreased in FWBP whereas GH levels remained unchanged in both FWBP and SWBP. Comparative analysis of gene profiles between FWBP and SWBP showed that pituitary prolactin transcript increased significantly in FWBP. Prolactin receptor (PRLR) transcripts increased in gill of FWBP while it decreased in gill and kidney of SWBP. NKA transcripts increased in gill of both FWBP and SWBP, while it decreased in intestine of FWBP and increased in intestine and kidney of SWBP. Glucocorticoid receptor (GR) transcripts decreased in intestine and kidney of FWBP while it increased in gill and intestine of SWBP. No significant changes were observed in growth hormone receptor (GHR) transcripts of both FWBP and SWBP in pituitary, gill, intestine and kidney. Our current data demonstrated the correlation between PRLR gene expression in relation to FW adaptation, and GR gene expression in relation to SW adaptation in euryhaline black porgy. The results indicate that black porgy has an excellent osmoregulatory capacity and is capable of withstanding large variations in salinity.