Anephric rats injected subcutaneously with urea in isotonic saline dra
nk much more than anephric control animals receiving isotonic saline a
lone. The pattern of water intake and urine output of normal rats, rep
eatedly injected with urea solution, was similar to that of rats injec
ted with dipsogenic hypertonic NaCl and quite different from that of r
ats receiving furosemide. A well-evident dipsogenic effect (unrelated
to the urine output) was observed in normal rats repeatedly injected w
ith 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 seru
m urea concentrations, the dipsogenic effect was present only initiall
y. These results demonstrate that urea exerts a direct dipsogenic acti
on which may be interpreted as a consequence of an osmotic gradient be
tween the extra- and the intracellular fluid. When this is positive, a
s in the case of a rapid rise of serum urea levels, cell dehydration e
nsues and thirst is stimulated. On the contrary, when serum urea level
s are decreasing and, presumably, when the intra- and the extracellula
r concentrations of urea are in equilibrium, no cellular dehydration o
ccurs and thirst does not appear.