This study was conducted to investigate the redistribution of fluid compartments and to examine the factors contributing to the variability of early weight loss in premature infants. Fourteen preterm infants (mean +/- SD: birth weight, 1473 +/- 342 gm; gestational age, 30.7 +/- 2.4 weeks) were studied at 1 and 7 days of age. Total body water was measured by deuterium oxide dilution, extracellular volume by bromide dilution, and intracellular volume by the difference between total body water and extracellular volume. There were significant changes in body fluid distribution per concurrent weight from birth to age 1 week. Extracellular volume decreased by 11%, and intracellular volume increased by 8.5% with no change in total body water. Infants were then grouped according to postnatal weight loss (group 1 (n = 7) > 10% and group 2 (n = 7) < 5% of birth weight). In group 1 there was a significant loss of both weight (mean +/- SD: 15.6% +/- 3.7%) and extracellular volume (15.9% +/- 9% of birth weight), with no change in intracellular volume. In group 2 there was no significant weight loss (1.4% +/- 1.8%), but a significant loss of extracellular volume (13.0% +/- 5.4% of birth weight) and a significant increase in intracellular volume. Other differences between the groups were a lower energy intake in group 1 than in group 2 (mean +/- SD: 177 +/- 46 vs 269 +/- 45 kilojoules/kg per day; p < 0.005) and a higher physiologic stability index in group 1 (p < 0.05). We conclude that significant postnatal weight loss as a result of the contraction of the extracellular compartment occurs only in less stable infants whose energy intake is inadequate. With adequate energy intake, weight loss is minimal because of the expansion of the intracellular compartment, which may be related to the onset of growth.