The aim of the study was a search of physiological approach to restoring osmotic homeostasis in rats with hypernatremia. Intraperitoneal administration of 1.8 ml/100 g BW 2.5% NaCl solution to Wistar rats induced hyperosmia (306 +/- 1 mOsm/kg H2O) and hypernatremia (150.3 +/- 0.3 mM in 60 min of experiment), increase in urinary sodium excretion (from 8 +/- 1 to 230 +/- 10 micromol/100 g BW for 2 h). Under these conditions enhancement of natriuresis up to 465 +/- 29 micromol/100 g BW and 667 +/- 24 micromol/100 g BW for 2 h was observed after injections of vasopressin analogue, deamino-vasotocin (dAVT, 0.05 microg/100 g BW), or loop diuretic, furosemide (1 mg/100 g BW), respectively. dAVT-induced natriuresis was accompanied by increase in solute-free water reabsorption; serum osmolality (301 +/- 1 mOsm/kg H2O) and sodium concentration (145.8 +/- 0.5 mM) were close to normal values by 60 min of experiment. Furosemide caused relatively greater excretion of water, than sodium; hypernatremia (150.2 +/- 0.4 mM) and hyperosmia (311 +/- 1 mOsm/kg H2O) persisted during 60 min of experiment. Thus, in rats with hypernatremia dAVT due to decrease in renal sodium reabsorption and increase in solute-free water reabsorption promotes recovery of serum osmolality and sodium concentration.