The aim of the present work was to study whole body protein synthesis and breakdown, as well as energy metabolism, in very low birth weight premature infants (< 1500 g) during their rapid growth phase. Ten very low birth weight infants were studied during their first and second months of life. They received a mean energy intake of 114 kcal/kg day and 3 g protein/kg day as breast milk or milk formula. The average weight gain was 15 g/ kg day. The apparent energy digestibility was 88%, i.e. 99 kcal/kg-day. Their resting postprandial energy expenditure was 58 kcal/kg-day, indicating that 41 kcal/kg day was retained. The apparent protein digestibility was 89%, i.e. 2.65 g/kg-day. Their rate of protein oxidation was 0.88 g/kg-day so that protein retention was 1.76 g/kg-day. There was a linear relationship between N retention and N intake (r= 0.78,p< 0.001). The slope of the regression line indicates a net efficiency of N utilization of 67%. Estimates of body composition from the energy balance, coupled with N balance method, showed that 25% of the gain was fat and 75% was lean tissue. Whole body protein synthesis and breakdown were determined using repeated oral administration of15N glycine for 60–72 h, and15N enrichment in urinary urea was measured. Protein synthesis averaged 11.2 g/kg-day and protein breakdown 9.4 g/ kg day. Muscular protein breakdown, as estimated by 3-methylhistidine excretion, contributed to 12% of the total protein breakdown. There was a positive correlation (r= 0.68,p< 0.05) between protein synthesis and protein gain, as well as between resting energy expenditure and protein gain (r= 0.58,p< 0.01). The slope of the regression line indicated that 1 g of protein gain required the synthesis of five times more protein (5 g) and resulted in an extra energy expenditure of 10 kcal. Thus, the net cost of protein synthesis in these very low birth weight infants was 2 kcal/ g.