The metabolic response to reduction in ambient temperature was studied in healthy, full-term, 1-d-old infants in Lima (50 m altitude, n = 20) and Cerro de Pasco (4,330 m, barometric pressure ~ 450 mm Hg, n = 20), Peru. Oxygen consumption (V̇O2) and carbon dioxide production (V̇CO2) were measured with an open-flow system as each infant rested quietly in a cylindrical humicrib, at wall temperatures of 35°C (warm) and 26°C (cool). The infants were exposed for 20 min to both temperatures, with the higher temperature followed by the lower, and oxygen consumption (V̇O2) and carbon dioxide production (V̇CO2) were measured over the last 8 min of each exposure. Average birth weight in Cerro de Pasco (2,933 ± 77 g [mean ± SE]) was less than in Lima (3,457 ± 73 g). In warm conditions, infants born at high altitude had slightly yet significantly lower body and skin temperatures than did those born at low altitude, with similar values of V̇O2 and heart rate (HR). Neither body nor skin temperature changed in either group during cooling. At low altitude, cooling increased V̇O2 (~ 34%), whereas no significant increase occurred in the high-altitude group. A similar response occurred for HR. Among several possibilities, the most likely interpretation of the results would be that of a decreased thermogenic capacity in the high- altitude infants because of the correspondingly lower oxygen availability during gestation.