To characterize the important changes in the selection and mobilization of metabolic fuel during cold stress, six males rested for 3 h at 29 degrees C and at 5 degrees C dressed only in shorts while 2H5 glycerol, 1-13C palmitate and 6,6 2H2 glucose were continuously infused for 3 h in each condition to determine their rate of turnover (Ra).Metabolic rate (M) as well as rates of carbohydrate (CHOox) and lipid oxidation (FATox) were assessed by indirect calorimetry whereas all isotopic enrichments were determined by mass spectrometry.Cold exposure decreased rectal and mean skin temperatures and increased M, FATox and CHOox compared with the same test at thermal neutrality (p<0.05). As expected, cold increased plasma glucose Ra and plasma FFA Ra (from 4.58+/-0.19 to 14.69+/-1.07 micromol kg(-1) x min(-1); p < 0.05). However, in absolute terms, plasma FFA Ra in the cold remained more than twice greater than FATox (FATox only increased up to 6.9 +/-0.85 micromol kg(-1) x min(-1)), suggesting an enhanced non-oxidative disposal of fatty acids (i.e., TG/FFA cycling) to account for all FFA Ra. Indeed, cold increased extracellular TG/FFA recycling rate (2.23+/-0.40 vs 7.77+/-1.19 micromol kg(-1) x min(-1); p<0.05) whereas intracellular cycling was unaffected.Even though lipolysis and FFA Ra are greatly increased by cold stress in humans, the present results demonstrate that only about half the rate of FFA Ra is ultimately oxidized, suggesting that under the present cold conditions: 1) non-oxidative FFA disposal or TG/FFA cycling is significantly enhanced; 2) white adipose tissue-derived fatty acids could easily account for most of FATox. The results further emphasize the importance of the TG/FFA cycle in amplifying the ability of stored TG to react quickly to major changes in energy expenditure induced by a sustained cold stress.