The energy intake, expenditure, and deposition of 40 breast-fed and formula-fed infants were investigated at 1 and 4 mo of age to explore possible differences in energy utilization between feeding groups. Energy intake was calculated from 5-d test-weighing records or pre- and postweighing of formula bottles, in combination with bomb calorimetry of the milks. Total daily energy expenditure (TDEE) was determined by the doubly labeled water method. Sleeping metabolic rate (SMR) and minimal observable energy expenditure were measured by indirect calorimetry. Activity was estimated as the difference between TDEE and SMR. Energy deposition was estimated from dietary intake and TDEE. Energy intakes were significantly higher for the formula-fed than breast-fed infants at 1 mo (118 ± 17 versus 101 ± 16 kcal/kg/d) and 4 mo (87 ± 11 versus 72 ± 9 kcal/kg/d) (p < 0.001). TDEE averaged 67 ± 8 and 64 ± 7 kcal/kg/d at 1 mo and 73 ± 9 and 64 ± 8 kcal/kg/d at 4 mo for the formula-fed and breast-fed infants, respectively, and differed between feeding groups ((p< 0.04). SMR and minimal observable energy expenditure (kcal/min) were higher among the formula- fed infants at 1 and 4 mo (p< 0.005). The energy available for activity and the thermic effect of feeding did not differ between feeding groups. Rates of weight gain (g/d) and energy deposition (kcal/kg/d) tended to be greater among the formula-fed infants at 1 and 4 mo ((p< 0.06). Differences in weight gain, energy deposition, SMR, minimal observable energy expenditure, and TDEE partially accounted for the discrepancy in energy intake observed between breast-fed and formula-fed infants. The response to the varying levels of energy intake in infancy appear to be mediated through growth and basal-energy-requiring processes, but not through physical activity.