Serial extracellular volume (ECV) changes were measured in 18 infants of less than 32 weeks gestation. Results were compared with changes in body weight, fluid and sodium intake, urine output, and serum sodium concentration. Mean +/- SD ECV decreased from 550 +/- 116 mL/kg on day 1 to 359 +/- 66 mL/kg on day 14. Thereafter, mean ECV/kg remained between 336 +/- 42 and 349 +/- 54 mL/kg. Clinical hydration and serum sodium concentration usually remained normal during this reduction of stabilization of ECV/kg. Six episodes of hyponatremia occurred at 11 to 31 days of age. Mean ECV/kg was significantly lower in infants with hyponatremia compared with infants of similar age with normal serum sodium concentration (303 +/- 36 mL/kg vs 368 +/- 56 mL/kg, P less than 0.01). Sodium intake in the two groups was similar. We conclude that ECV in the VLBW infant decreases postnatally and is regulated within a range similar to that in older infants, and that postnatal natriuresis in the first 2 weeks of life represents physiologic reduction of the expanded ECV of the fetus. Late hyponatremia may indicate excessive sodium loss and ECV depletion.