1. Watery vacuolation in the acinar cells of the rat submandibular gland is described. The vacuoles are cytoplasmic, membrane-walled, and 2-20 mu in diameter. They are visible in living cells and appear to contain a watery fluid.2. Vacuolation occurred regularly in the following experimental situations: (1) in vitro-under anoxic conditions (2) post mortem-in animals killed by anoxia, and (3) in vivo-during secretion.3. By in vitro experiments it was shown that vacuolation occurs only when the cells are both anoxic and exposed to an excess of extracellular fluid containing calcium and bicarbonate. It was further shown that vacuolation is reversible in oxygen and that both its development and recovery are temperature dependent.4. Evidence is presented that the vacuolation is not a degenerative or necrotic change, that it is accompanied by the entry of fluid into the cells, and that it is not caused by simple osmosis.5. The mechanism of vacuolation and its possible relation to secretion are discussed. It is suggested that vacuolation represents an imbalance between the ingestion and secretion of water and salts.6. Similar vacuoles, apparently produced by the same mechanism, were observed in the acinar cells of the parotid gland and the pancreas of the rat.7. The close similarity of this vacuolation to that previously described in rat liver cells was noted.