It has recently become evident that maintenance of ionic homoeostasis in euryhaline salmonids involves a reciprocal shift in expression of two isoforms of the gill NaC,KC-atpase a-subunit when the surrounding salinity changes. The present study investigated the regulation of this shift between the a1a (freshwater (FW) isoform) and the a1b seawater (SW) isoform) by cortisol, Gh, prolactin (Prl) and Igf 1. Injection with cortisol into FW salmon increased a1a expression, while Gh had no effect. Conversely, both cortisol and Gh stimulated a1b expression, and a significant synergy was observed. igf1 expression was increased by Gh in both gill and liver, and inhibited by cortisol in the liver. Gill Igf1 and Gh receptor expression increased in response to cortisol. Injection with Prl into SW salmon compromised their hypo-osmoregulatory performance, selectively reduced the expression of the a1b isoform and decreased enzymatic NaC,KC-atpase activity in the gill. Cortisol and Prl reduced gill and liver igf1 expression, and both hormones stimulated gill Igf1 receptor expression. In a short-term experiment with incubation of FW gill cell suspensions, cortisol stimulated a1a and a1b expression, while Igf1 stimulated only a1b. The data elaborate our understanding of Prl and Gh as being antagonists in the control of gill ion regulation, and support a dual role for Gh involving endocrine and paracrine Igf1 action. Gh and Prl may be the decisive stimuli that direct cortisol-aided mitochondrion-rich cell development into either secretory or absorptive types.