Ammonia is toxic to all vertebrates. It can be converted to the less toxic urea, but this is a metabolically expensive process found only in terrestrial vertebrates that cannot readily excrete ammonia and marine fish that use urea as an osmotic filler. Freshwater fish mostly excrete ammonia with only a small quantity of urea. It seems the ornithine cycle for urea production has been suppressed in all freshwater teleosts except for some airbreathers which, when exposed to air, increase urea synthesis via the cycle. Here we show that the tilapia fish Oreochromis alcalicus grahami, the only fish living in Lake Magadi, an alkaline soda lake (pH = 9.6-10) in the Kenyan Rift Valley, excretes exclusively urea and has ornithine-urea cycle enzymes in its liver. A closely related species that lives in water at pH 7.1 lacks these enzymes and excretes mainly ammonia with small amounts of urea produced via uricolysis. It dies within 60 min when placed in water from Lake Magadi. We suggest that urea production via the ornithine-urea cycle permits O. a. grahami to survive the very alkaline conditions in Lake Magadi.