Late hyponatremia (plasma Na+ less than 130 mEq/liter) occurred frequently (on 54 of 159 occasions) in 46 very low virthweight (VLBW) infants (less than 1.3 kg at birth) between 2 and 6 weeks of age while receiving a sodium intake of less than or equal to 2 mEg/kg/24 hr. To elucidate possible pathogenetic mechanisms five groups of such infants were studied while receiving a commercially available formula reconstituted to give two different volumes and two different Na+ concentrations. Sodium intake in the nonsupplemented (NS) infants (n = 23) was less than 2 mEq/kg/24 hr. Supplemented (S) infants (n = 16) received approximately 3 mEq Na+/kg/24 hr. A further group of seven infants given a high volume (200 ml/kg/24 hr), high caloric (100 cal/dl) formula and Na+ supplementation (to 3 mEq/kg/24 hr) was also included. Infants were studied from age 14 days until they weighed 1.80 +/- 0.05 kg at a mean age of 47 days. At the time of start of the study, 6 of 20 NS and 6 of 19 S infants were hyponatremic. After supplementation only two episodes of hyponatremia occurred in S infants, both during the first study week, whereas the high incidence of hyponatremia in NS infants period. During baseline urine collections all infants excreted between 80 and 100 ml/kg/24 hr urine, but those receiving 150 ml/kg/24 hr formula decreased their urinary output rapidly to 50 ml/kg/24 hr, whereas infants receiving high volume feeds (200 ml/kg/24 hr) did not decrease their urinary output until the third balance at an average age of 45 days. All infants excreted between 1.0 and 1.2 mEq/kg/24 hr of sodium in their urine during the initial collection. Nonsupplemented infants reduced their urinary Na+ excretion more rapidly than supplemented babies (NS: from 1.03 to 0.55 mEq/kg/24 hr, first vs second balance; S: from 1.00 to 0.80 mEq/kg/24 hr, first vs third balance). Mean potassium excretion remained unchanged in NS and S infants during the study period and was not affected by the volume or caloric content of the formula. Extracellular volume (ECV) and total body water (TBW) were measure serially, and there were no differences between S and NS infants in the distribution of body water. The percentage of TBW and ECV decreased in all groups with increasing postnatal age.