To determine whether body weight during the first 2 weeks of life in preterm infants weighing less than 1500 gm reflects nutritional status or fluid balance, we studied total body water (TBW) (deuterium oxide dilution), extracellular volume (sucrose dilution), and plasma volume (Evans blue dilution), together with intake-output studies of nitrogen, fluid, and sodium on day 1 (median age 0.3 day), at a weight loss of 7.8% of birth weight (median age 3.4 days), and after birth weight was regained (median age 8.9 days) in eight clinically stable preterm infants (birth weight 810 to 1310 gm, gestational age 26 to 30 weeks) receiving ventilatory support. During the initial weight loss we found no evidence of catabolism. Body solids (weight--TBW) remained unchanged, there was nitrogen retention, and energy intake was sufficient to meet energy expenditure by day 2. However, we found evidence of fluid loss: TBW (mean +/- SD, -95 +/- 99 ml), extracellular volume (-98 +/- 63 ml), and interstitial volume (-102 +/- 75 ml) decreased significantly, indicating negative fluid and sodium balances. Blood volume and plasma volume remained unchanged. With the regaining of birth weight there was no increase in body solids despite a high degree of nitrogen retention, but there was a positive fluid balance although no significant increase in any body fluid compartment was found. We conclude that the observed postnatal weight changes reflect changes in interstitial volume.