We prospectively evaluated the frequency, cause, and outcome of hyponatremia (plasma sodium concentration, less than 130 meq/L), as well as the hormonal response to this condition, in hospitalized patients. Daily incidence and prevalence of hyponatremia averaged 0.97% and 2.48%, respectively. Two thirds of all hyponatremia was hospital acquired. Normovolemic states (so-called syndrome of inappropriate secretion of antidiuretic hormone) were the most commonly seen clinical setting of hyponatremia. The fatality rate for hyponatremic patients was 60-fold that for patients without documented hyponatremia. Nonosmotic secretion of vasopressin was present in 97% of hyponatremic patients in whom it was sought. In edematous and hypovolemic patients, plasma hormonal responses (increases in plasma renin activity and aldosterone and norepinephrine levels) were compatible with baroreceptor-mediated release of vasopressin. Hyponatremia is a common hospital-acquired electrolyte disturbance that is an indicator of poor prognosis. Nonosmotic secretion of arginine vasopressin is a major pathogenetic factor in this electrolyte disturbance.