Severe hyponatremia occurs in some patients with untreated hypopituitarism, but it is not known whether such hyponatremia is caused by the hypersecretion of vasopressin (antidiuretic hormone). This report describes severe, symptomatic hyponatremia in five women 59 to 83 years old (serum sodium, 111 to 118 mmol per liter) who presented with hypopituitarism (which had been previously undiagnosed in four). Plasma vasopressin was inappropriately high (1.3 to 25.8 pmol per liter [1.4 to 28 ng per liter]) in relation to plasma osmolality (236 to 260 mOsm per kilogram of body weight). All five patients had normal renal function and no signs of dehydration or volume depletion. The hyponatremia was resolved within a few days after the institution of hydrocortisone therapy, after infusion of normotonic or hypertonic saline had been found to be less effective. When four of the patients were later restudied while receiving maintenance hydrocortisone treatment, the relation between plasma vasopressin and osmolality was normal. We conclude that ACTH deficiency may cause the syndrome of inappropriate secretion of antidiuretic hormone. The beneficial effect of hydrocortisone is probably exerted through the suppression of vasopressin secretion.