By the combination of energy and macronutrient balances, continuous open circuit computerized indirect calorimetry, and anthropometry, we have compared small for gestational age (SGA) and appropriate for gestational age (AGA) very low birthweight infants with respect to metabolizable energy intake (mean +/- SE: 125.9 +/- 2.5 versus 130.4 +/- 3.5 kcal/kg X day), energy expenditure (67.4 +/- 1.3 versus 62.6 +/- 0.9 kcal/kg X day), storage of energy and macronutrients and growth. Fourteen studies in six SGA infants (gestational age, 33.1 +/- 0.3 weeks; birthweight, 1120 +/- 30 g) and 22 studies in 13 AGA infants (gestational age, 29.3 +/- 0.4 weeks; birthweight, 1155 +/- 40 g) were performed. The SGA infants had a lower absorption of fat (68.7 +/- 3.2 versus 79.7 +/- 1.7%) and protein (69.1 +/- 3.2 versus 83.4 +/- 1.5%) and hence increased (P less than 0.001) energy loss in excreta (29.9 +/- 2.8 versus 18.2 +/- 1.5 kcal/kg X day). The significant hypermetabolism of SGA infants by 4.8 kcal/kg X day was associated with an increased fat oxidation. Despite lower energy storage, SGA infants were gaining weight (19.4 +/- 0.9 g/kg X day), length (1.25 +/- 0.14 cm/week), and head circumference (1.16 +/- 0.9 cm/week) at higher rates than the AGA group. The energy storage per g weight gain was lower (P less than 0.001) in the SGA group (3.0 +/- 0.14 versus 4.26 +/- 0.26 kcal) reflecting higher water, lower fat (22.2 +/- 1.8 versus 33.8 +/- 2.5%; P less than 0.001) and lower protein (7.7 +/- 0.5 versus 12.5 +/- 0.8%; P less than 0.001) contents of weight gain in the SGA group.