Migration of sodium out of body cells has been assumed to account for discrepancies observed between total losses of this ion from the body and changes in the sodium content of the extracellular compartment. To study this concept a ‘pure’ sodium deficiency was produced acutely in dogs by means of vivodialysis, resulting in the removal of approximately 23% of total body sodium. Analyses of plasma, muscle, skin, tendon, bone, heart and liver for water and electrolytes were performed before, during and after the procedure. It was found that the extracellular phase of the body contributed 70%, bone mineral 25% and body cells only 5% of the total sodium removed. The relative rates of removal of sodium from various tissues were compatible with their known vascularity and water content, with the exception of bone mineral. Highly vascular tissues, such as muscle and skin, had a rapid initial rate of sodium removal which declined with time, as sodium stores were rapidly depleted. Avascular tissues, as exemplified by tendon, showed an increasing rate of sodium removal with time, as equilibration became more complete. Removal of this fraction of total body sodium resulted in a severe, uncompensated, metabolic acidosis. Despite relatively small changes in plasma electrolytes, hypotension, vascular collapse and, in some cases, death occurred in these animals. A new hypothesis, based on current concepts of bone crystalline structure, is presented to account for the falling rate of sodium removal from bone mineral as contrasted with the increasing rate of removal from other avascular tissues.