1. A culture of Tetrahymena pyriformis adapted to a high NaCl medium, containing 220 mM NaCl, was investigated. The concentration of NaCl in the medium of the normal (unadapted) animals was about 35 mM. 2. Upon direct transfer to the high NaCl medium, only 2% of the normal cells were sufficiently tolerant of the stress to survive and divide. Data were presented indicating that stress tolerance is a heritable character, and that this character was selected for upon transfer to the high NaCl medium. 3. The cell volume of the adapted cells was 45% less than that of the normal animals. The adapted cells were more nearly spherical than normal cells. Despite the smaller size of the adapted cells, the amount of non-volatile material per cell was the same in normal and adapted cells. 4. The main feature of the adaptation was a greatly increased ability of adapted cells to maintain a low cellular salt concentration. Sodium concentration in normal cells in normal medium was 13 meq./l. of cells. Sodium concentration in normal cells equilibrated in high NaCl medium was 105 meq./l. of cells. Sodium concentration in adapted animals was 43 meq./l. of cells two weeks after starting the culture, and fell gradually to 21 meq./l. of cells in 1500 generations (22 months). This constituted selection for ability to regulate sodium. 5. Two major differences in sodium regulation between normal and adapted cells were observed. First, the saturation level of the sodium extrusion mechanism, 20 mM in normal cells, increased to 120 mM in the adapted cells. Secondly, the "apparent free spaces" of both sodium and chloride were lower in adapted than in normal cells. The increased ability to regulate cellular sodium in adapted cells was held not to be due to a decrease in permeability to sodium. 6. From experiments utilizing an isotopic tracer, Na24, 70% of cellular sodium was shown to be readily exchangeable with external sodium. 7. Potassium regulation was altered with adaptation such that potassium concentration per unit volume was the same in normal and adapted cells. The striking similarity of cellular potassium concentrations in Tetrahymena and a variety of other lower fresh-water invertebrates was pointed out. These points were discussed with respect to a general minimum protoplasmic potassium concentration.