We assessed sodium balance and extracellular volume regulation in very low birth weight infants by examining the effect of differences in sodium intake on postnatal sodium homeostasis and body water composition. Twenty infants (mean birth weight 1103 +/- 216 gm, mean gestation 28.5 +/- 1.7 weeks) were randomly assigned to receive sodium in doses of either 1 or 3 mmol.kg-1.day-1 for the first 10 postnatal days. Extracellular volume (estimated by the bromide dilution method), sodium excretion, creatinine clearance, fractional sodium excretion, plasma atrial natriuretic factor level, urine aldosterone concentration, and vasopressin excretion were measured on postnatal days 1, 5, 10, 20, and 30. The corrected bromide space was large at birth and decreased in both groups during the first 5 days of observation, concomitant with a negative sodium balance. After 5 days of age, sodium excretion decreased in both groups so that sodium balance became positive and the corrected bromide space increased in proportion to increasing body weight. Differences in sodium intake were associated with differences in tubular sodium reabsorption; corrected bromide space and net sodium balance were similar in the two groups. Serum sodium concentration was significantly lower in the low-sodium intake group. Creatinine clearance, plasma atrial natriuretic factor level, and excretion of aldosterone and vasopressin were not significantly different between the two groups. We conclude that very low birth weight infants are able to regulate sodium balance by altering renal sodium excretion. However, the renal response to sodium intake may be insufficient to prevent changes in serum sodium concentration. The roles of specific renal and hormonal mechanisms regulating sodium excretion in very low birth weight infants remain incompletely defined.