1. Simultaneous measurements of exchangeable Na+, exchangeable K+, extracellular fluid volume and total body water, with 24Na, 43K, 77Br and 3H2O, were carried out in patients with adrenocortical insufficiency due to pituitary ablation performed 1–3 months previously.
2. The first group of five patients was studied before and after withdrawal of maintenance prednisone (2·5 mg three times daily, orally). The effects of glucocorticoid withdrawal were: (a) an increase in intracellular water (all cases) and a decrease in the extracellular fluid volume (four cases) irrespective of any change in serum Na+ concentration; (b) an increase in residual (‘intracellular’) Na+ in all cases which was matched by a loss of extracellular Na+, so that total body Na+ remained unchanged, and (c) the cortisol deficiency clinical syndrome. Exchangeable K+ remained unchanged.
3. Similar measurements were obtained with two further patients during the corticosteroid withdrawal period, throughout which they were kept on a maintenance dose of deoxycorticosterone acetate, 1·0 mg twice daily sublingually. Neither the above biochemical changes nor the cortisol deficiency syndrome developed.
4. The shift into the cells of water and Na+ may depend on the same defect caused by glucocorticoid deficiency, and may be the cause of the cortisol deficiency syndrome.