High levels of hybridization between Atlantic salmon Salmo salar and brown trout Salmo trutta have been reported in the River Driva. This study presents the underlying mechanisms of development of seawater (SW) tolerance and marine migration pattern for S. salar×S. trutta hybrids. Migrating S. salar×S. trutta hybrid smolts caught in the River Driva, Norway (a river containing Gyrodactylus salaris), displayed freshwater (FW) gill Na+, K+-ATPase (NKA) activity levels of 11·8 µmol ADP mg protein h−1, which were equal to or higher than activity levels observed in S. salar and S. trutta smolts. Following 4 days of SW exposure (salinity 32·3), enzyme activity remained high and plasma ion levels were maintained within the normal physiological range observed in S. salar smolts, indicating no signs of ion perturbations in S. salar×S. trutta hybrids. SW exposure induced an increase in NKA α1b-subunit mRNA levels with a concurrent decrease in α1a levels. Salmo salar×S. trutta post-smolts migrated rapidly through the fjord system, with increasing speed with distance from the river, as is often seen in S. salar smolts. The present findings suggest that S. salar×S. trutta smolts, as judged by the activity and transcription of the NKA system, regulation of plasma ion levels and migration speed more closely resemble S. salar than S. trutta.