The frequency and pathophysiology of hyponatremia were studied in the acquired immunodeficiency syndrome. Of 71 hospitalized patients surveyed retrospectively, hyponatremia was observed in 37 (52%). Of 48 patients studied prospectively, 27 (56%) were hyponatremic. In 16 hyponatremic patients, volume status; serum and urine osmolalities; renal, adrenal, and thyroid function; and plasma vasopressin levels were assessed. Urine osmolalities were inappropriately elevated (mean, 377 mmol/kg of water) relative to serum osmolalities (mean, 268 mmol/kg of water). Four patients had moderate renal insufficiency. Plasma vasopressin levels were elevated in 15 patients, with the highest levels seen in patients who died (median, 7.08 pmol/L). Hyponatremia of multiple etiologies occurred in a majority of inpatients with the acquired immunodeficiency syndrome, often following the administration of hypotonic fluids, and was associated with a 30% (8/27) short-term mortality.