Dexamethasone is commonly administered to ventilator-dependent preterm infants with chronic lung disease. Infants receiving dexamethasone therapy frequently exhibit decreased rates of weight gain. The purpose of this investigation was to determine whether decreased growth in infants receiving dexamethasone therapy is caused by increased energy expenditure. Twelve infants were studied: 6 received dexamethasone treatment at 2 wk of age and crossed over to receive placebo treatment at 4 wk; the treatment order was reversed in the other 6 infants. The doubly labeled water method was used to determine energy expenditure for a 1-wk period during each treatment phase. The rate of weight gain during dexamethasone treatment was 6.5+/-10.6 and 20.0+/-5.7 g/kg/d during placebo treatment. Energy expenditure was 93.1+/-34.6 kcal/kg/d during dexamethasone treatment and 88.3+/-37.1 kcal/kg/d during placebo treatment. Energy intake was 119.2+/-29.0 kcal/kg/d during dexamethasone treatment and 113.8+/-23.7 kcal/kg/d during placebo treatment. The difference between intake and expenditure, or the energy available for growth, was 26.2+/-36.8 kcal/kg/d during dexamethasone treatment and 25.5+/-37.4 kcal/kg/d during placebo treatment. No significant differences were found in energy expenditure or energy intake between the treatment phases. The reduced growth seen in infants receiving dexamethasone treatment cannot be explained by increased energy expenditure or decreased energy intake, but may be due to differences in the composition of newly accreted tissue.