Freshly drawn heparinized human whole blood is exposed to x-rays in amounts up to 54,000 r in vitro and then equilibrated under a controlled atmosphere at 24 or 38 degrees C. For as long as 26 hours following exposure, potassium is progressively lost from the cells and quantitatively replaced by sodium with little, if any, osmotic disturbance. The mean rate of loss at 20,000 r and 24 degrees C. is about 0.4 per cent of the initial cell potassium per hour and approximately doubles for a 20,000 r increase. It is accentuated if blood is stored at low temperature (5 degrees C.) following radiation exposure. Isotope experiments show that the rate of entrance of potassium into the cells is practically unaltered, the principal effect being an acceleration of the rate from cells to plasma. This suggests that radiation may have interfered with a mechanism of selective potassium accumulation based on preferential retention of the element. The sodium which enters the cells following irradiation contributes to the rapidly exchanging portion of the cellular sodium, suggesting that this fraction is ionic sodium.