Anephric rats injected subcutaneously with urea in isotonic saline drank much more than anephric control animals receiving isotonic saline alone. The pattern of water intake and urine output of normal rats, repeatedly injected with urea solution, was similar to that of rats injected with dipsogenic hypertonic NaCl and quite different from that of rats receiving furosemide. A well-evident dipsogenic effect (unrelated to the urine output) was observed in normal rats repeatedly injected with urea solution and having a rapid rise of serum urea concentrations. On the contrary, in rats receiving a single load of urea and showing first a very rapid increase, then followed by a slow decrease of serum urea concentrations, the dipsogenic effect was present only initially. These results demonstrate that urea exerts a direct dipsogenic action which may be interpreted as a consequence of an osmotic gradient between the extra- and the intracellular fluid. When this is positive, as in the case of a rapid rise of serum urea levels, cell dehydration ensues and thirst is stimulated. On the contrary, when serum urea levels are decreasing and, presumably, when the intra- and the extracellular concentrations of urea are in equilibrium, no cellular dehydration occurs and thirst does not appear.