To compare the growth and accumulation of protein, fat, and carbohydrate in the formula-fed premature infant and in the fetus of a similar postconceptional age, we performed 22 metabolic studies in 13 infants of very low birth weight (1155 +/- 39 g [mean +/- S.E.]). Measurements combining nutritional balance and indirect calorimetry demonstrated the deposition rates of protein and fat. We found that the formula-fed, very-low-birth-weight infant who gained weight comparably to the fetus retained the same amount of protein (1.92 +/- 0.1 g per kilogram of body weight per day) but accumulated fat at a rate of 5.4 +/- 0.3 g per kilogram per day - about three times that in the fetus, as confirmed by increased skin-fold thickness. How this change in body composition affects the future growth of formula-fed premature infants, and how body composition is altered by other dietary regimens such as the provision of human milk, remain to be determined.