Our study aimed to characterize the influence of changes of extracellular osmolarity on renin secretion from the whole kidney. For this purpose the osmolarity of the perfusion medium of isolated rat or mouse kidneys was either decreased by lowering the NaCl-concentration by 20% or was increased up to 133% by the addition of various salts or sugars. It turned out that changes of osmolarity led to instantaneous transient changes followed by a plateau of renin secretion, in the way that increases of osmolarity stimulated renin secretion, whilst decreases attenuated renin secretion. The peak amplitude of changes of renin secretion was related to steady state renin secretion rates prior to the osmotic challenge but was independent on the maneuver used to modulate steady state renin secretion. Osmolarity induced changes of renin secretion were more related to relative rather than to absolute changes of osmolarity and were not dependent on the formation of nitric oxide or of prostanoids and did not require Na-K-2Cl cotransport function or swelling activated chloride channels. Moreover, we obtained evidence, that the pool of renin secretion excitable by hyperosmolarity is exhaustible and that its complete refilling takes at least two minutes. The observed behavior of renin secretion fits into the concept about exocytosis proposing the existence of different pools of committed secretory vesicles, which have not yet undergone the final modification for initiation of exocytosis. Probably a pool of readily releasable vesicles determines steady state secretion rates from kidneys.