Injection of solutes such as Na+ or mannitol, which initially elevate ECF osmotic pressure and then draw water from cells to dilute the load to near isotonicity, causes reliable drinking in all species studied. This osmoregulatory drinking is accompanied by report of thirst in humans and secretion of AVP. The threshold elevation of systemic osmolality to initiate these changes is in the range 1–3%. Regardless of whether drinking is allowed, the osmotic load is excreted by the kidney over the course of2–4 hours. From sham drinking and other studies, osmoregulatory drinking is satiated when osmotic pressure is normalized and cellular water is restored. Many studies have shown that osmoreceptors for drinking and AVP secretion are located in or near the CVOs of the lamina terminalis. In addition, peripheral osmoreceptors in the gut or splanchnic regions monitor the osmolality of fluids absorbed from the gut and are sufficient to stimulate drinking in the absence of systemic hyperosmolality.