In teleosts, cortisol is one of the key factors regulating the adaptation to environmental challenges, such as salinity changes. This paper compares interrenal function between fully adapted freshwater (FW) and sea water (SW) specimens of the euryhaline teleost Oreochromis mossambicus (tilapia), combining morphometric and biosynthetic approaches. Interrenal tissue and two tissues producing interrenal secretagogues (ACTH and A N P; atrial natriuretic peptide) were studied. The results demonstrate that sea water adaptation concurs with a sustained stimulation of the interrenal cells, as evidenced by a marked hyperplasia of the cells and the higher initial ex vivo cortisol release in seawater adapted tilapia. This difference was not reflected in ultrastructural differences in the pituitary corticotropes. Plasma ACTH levels were also similar in FW and SW adapted tilapia. Moreover, in vitro data indicate that the A C T H sensitivity of the interrenal cells of both groups was also similar. A second potential interrenal secretagogue (ANP) has recently been implicated in teleost ionic regulation during salinity changes. However, plasma immunoreactive A N P levels and in vitro production of the hormone were also indistinguishable between FW and SW tilapia. A N P pretreatment of tilapia head kid neys in vitro strongly inhibited the response to A C T H , an effect previously undocumented for teleosts.Whereas the sustained stimulation of the interrenal cells under sea water conditions corroborates results obtained with other teleost species, thereby supporting a hypoosmoregulatory role for cortisol, it also is evident that notable species differences exist regarding the regulation of the interrenal gland under these conditions.