To determine if concentration of plasma arginine vasopressin (AVP) is inappropriate for the plasma Na+concentration in hyponatremic burned patients, we obtained 32 plasma samples from 20 patients with total burn size (TBS) 15 to 80% of body surface on or after postburn day (PBD) 4 in the morning following all-night recumbency. In the 25 samples (17 patients) with hyponatremia, AVP was elevated, 1.6 to 14.3 (normal < 0.5) pg/ml. Most patients with normal serum Na+had normal AVP values. Out of the total, nine patients (12 samples) without renal failure or sepsis, selected also for hyponatremia and urinary Na+≥ 20 mEq/L, were considered separately. BUN of 11.7 ± 1.8 mg/dl and plasma glucose of 130 ± 5.6 mg/dl, Na+of 130 ± 1.1 mEq/L, calculated osmolality of 272 ± 1.6 mosm/kg, and cortisol of 20.4 ± 1.6 μg/dl were associated with a 24-hour fluid intake of 4.3 ± 0.26 L and urinary output of 2.7 ± 0.33 L, Na+of 80 ± 14 mEq/L, and osmolality of 520 ± 73 mosm/kg (mean ± SE). In all of the plasma samples, AVP was markedly elevated (6.9 ± 1.1 pg/ml). In another study, four hyponatremic burned patients were given a standard water load. Excretion of the water was delayed, and further dilution of the initially hypotonic plasma resulted in a fall of urinary osmolality and plasma AVP. Cutaneous thermal injury can cause resetting of the mechanism linking plasma tonicity and AVP secretion resulting in dilutional hyponatremia. This syndrome occurs in the absence of gross physiologic perturbations such as volume depletion or adrenal insufficiency.