We investigated the physiological mechanisms involved in central hyponatraemia in patients with acute craniocerebral injury (ACI). We measured blood concentrations of natriuretic peptides, antidiuretic hormone (ADH), and endogenous digitalis-like substance (EDLS), blood and urine sodium concentrations, and the plasma and urine osmolality in 68 patients with ACI and 24 healthy control subjects. A total of 27 ACI patients were hyponatraemic and the majority of these had grievous or severely grievous craniocerebral injuries. Blood concentrations of EDLS and ADH in hyponatraemic ACI patients were significantly higher compared with normonatraemic ACI patients and control subjects. Blood EDLS and sodium concentrations were negatively correlated with each other, whereas EDLS was positively correlated with urine sodium concentration and with urine osmotic pressure. Hyponatraemic ACI patients require different treatment based on the cause of their central hyponatraemia, so it is important to undertake a comprehensive analysis of each patient's physiological status.