To investigate the energy requirements of infants living under unfavorable environmental conditions in rural Mexico, we measured the total energy expenditure (TEE) of 40 Otomi infants at approximately 4 or approximately 6 mo of age. Total energy expenditure was estimated by the doubly labeled water method: 100 mg 2H2O/kg and 250 mg 18O/kg were administered orally, after which urine was collected serially for 7 or 10 d. Isotopic enrichment of urine samples was analyzed by gas-isotope-ratio mass spectrometry. Weight and length were measured monthly from birth to 6 mo. Fat free mass was estimated from 18O dilution spaces. Total energy expenditures (mean +/- SD) were 310 +/- 58 and 318 +/- 29 kJ.kg-1 x d-1 at approximately 4 and approximately 6 mo, respectively. Total energy expenditure was higher than that previously observed for breast-fed infants reared under more protected environments (268 +/- 29 kJ.kg-1 x d-1). Weight, length and weight gain were 5.9 +/- 0.8 kg, 60 +/- 2 cm and 2.9 +/- 2.4 g.kg-1 x d-1 at 4.25 mo and 7.1 +/- 0.8 kg, 65 +/- 2 cm and 1.0 +/- 1.2 g.kg-1 x d-1 at 6.27 mo. Growth faltering was evident at 6 mo by clinically significant declines in growth velocities and National Center for Health Statistics Z-scores. Body fat of the Otomi infants averaged 21 +/- 6 and 18 +/- 5 g/100 g at approximately 4 and approximately 6 mo, respectively. Higher rates of TEE narrowed the margin of energy available for growth and thereby contributed to growth faltering in the Otomi infants.