Hyponatremia secondary to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a frequent cause of hypotonicity. Although the differential diagnosis with other causes of hypotonicity such as salt depletion is sometimes challenging, some simple and readily available biologic parameters can be helpful in the diagnosis of SIADH. In SIADH, urea is typically low; this is less specific for elderly patients, for whom lower clearance of urea accounts for higher values. Low levels of uric acid are more often seen in SIADH (70%) compared with salt-depleted patients (40%). Typically, patients with SIADH will show a lower anion gap with nearly normal total CO2 and serum potassium, this despite dilution. In patients with hyponatremia secondary to hypocorticism, total CO2 is usually lower than in nonendocrine SIADH despite low urea and uric acid levels. Urine biology can also be helpful in diagnosis of SIADH because patients with SIADH have high urine sodium (Na; >30 mEq/L), and most of them will have a high fractional excretion of Na (>0.5% in 70% of cases), reflecting salt intake. Conversely, low urine Na in patients with SIADH and poor alimentation is not rare. Finally, measurement of urine osmolality is useful for the diagnosis of polydipsia and reset osmostat and could further help in the choice of therapeutic strategy because patients with low urine osmolality will benefit from water restriction or urea, whereas those with high urine osmolality (>600 mOsm/kg) would be good candidates for V2 antagonist.