-Volume homeostasis is essential for the preservation of lens transparency and this is of particular significance to anadromous fish species where migration from freshwater to seawater presents severe osmotic challenges. In Atlantic salmon (Salmo salar L.), aqueous humor (AH) osmolality is greater in fish acclimated to seawater compared with young freshwater fish, and levels of lens N-acetylhistidine (NAH) are much higher in seawater fish. Here we investigate NAH as an osmolyte in the lenses of salmon receiving diets either with or without histidine supplementation. In the histidine-supplemented diet (HD) histidine content was 14.2 g/kg, and in the control diet (CD) histidine content was 8.9 g/kg. A transient increase in AH osmolality of 20 mmol/kg was observed in fish transferred from freshwater to seawater. In a lens culture model, temporary decreases in volume and transparency were observed when lenses were exposed to hyperosmotic conditions. A positive linear relationship between extracellular osmolality and lens NAH content was also observed, whereas there was no change in lens histidine content. Hypoosmotic exposure stimulated [ 14 C]-histidine efflux by 9.2-and 2.6-fold in CD and HD lenses, respectively. NAH efflux, measured by HPLC, was stimulated by hypoosmotic exposure to a much greater extent in HD lenses. In vivo, lens NAH increased in response to elevated AH osmolality in HD but not CD fish. In conclusion, NAH has an important and novel role as a compatible osmolyte in salmon lens. Furthermore, it is the major osmolyte that balances increases in AH osmolality when fish move from freshwater to seawater. A deficiency in NAH would lead to a dysfunction of the normal osmoregulatory processes in the lens, and we propose that this would contribute to cataract formation in fish deficient in histidine. histidine PREVALENCE OF CATARACT IN farmed Atlantic salmon (Salmo salar L.) has increased in recent years (3) and this has been linked to the removal of a rich source of dietary histidine (blood meal) (7). Several recent studies have investigated the possible causes of cataract in farmed salmon (6, 9, 30), although the mechanisms involved remain to be elucidated.Osmotic stress has been shown to contribute to cataract formation in multiple species, including man (19). Efficient volume regulation is crucial for the maintenance of lens transparency and disruption to the tightly packed and highly ordered cells and proteins that make up the lens will cause a loss of lens transparency. In fish there are numerous examples where osmotic factors have been shown to play a role in cataract development (20), and the anadromous life cycle of the Atlantic salmon exposes the fish to particularly severe osmotic stress. The early part of salmon development is spent in freshwater as parr followed by transformation to smolts before entering the sea. Despite the physiological changes associated with parr-smolt transformation, a preadaption for life in seawater, reversible osmotic cataracts, are commonly described immediately aft...