-We hypothesized that reliance on lactate as a means of energy distribution is higher after a prolonged period of acclimatization (9 wk) than it is at sea level due to a higher lactate R a and disposal from active skeletal muscle. To evaluate this hypothesis, six Danish lowlanders (25 Ϯ 2 yr) were studied at rest and during 20 min of bicycle exercise at 146 W at sea level (SL) and after 9 wk of acclimatization to 5,260 m (Alt). Whole body glucose R a was similar at SL and Alt at rest and during exercise. Lactate R a was also similar for the two conditions at rest; however, during exercise, lactate R a was substantially lower at SL (65 mol ⅐ min Ϫ1 ⅐ kg body wt Ϫ1 ) than it was at Alt (150 mol ⅐ min Ϫ1 ⅐ kg body wt Ϫ1 ) at the same exercise intensity. During exercise, net lactate release was ϳ6-fold at Alt compared with SL, and related to this, tracer-calculated leg lactate uptake and release were both 3-or 4-fold higher at Alt compared with SL. The contribution of the two legs to glucose disposal was similar at SL and Alt; however, the contribution of the two legs to lactate R a was significantly lower at rest and during exercise at SL (27 and 81%) than it was at Alt (45 and 123%).In conclusion, at rest and during exercise at the same absolute workload, CHO and blood glucose utilization were similar at SL and at Alt. Leg net lactate release was severalfold higher, and the contribution of leg lactate release to whole body lactate R a was higher at Alt compared with SL. During exercise, the relative contribution of lactate oxidation to whole body CHO oxidation was substantially higher at Alt compared with SL as a result of increased uptake and subsequent oxidation of lactate by the active skeletal muscles.glucose; isotopes; [1-13 C]lactate CARBOHYDRATE AND LACTATE METABOLISM is altered by hypoxia. Carbohydrate oxidation under hypoxic conditions has been suggested to be the preferable metabolic pathway during exercise, because it provides the highest ATP yield per mole of oxygen (3,15,16). Thus any increase in the percentage of energy derived from carbohydrate sources will result in a more economical use of oxygen. Indeed, results from studies in high-altitude natives (17) and lowlanders exposed to high altitude (5, 27) show a shift toward increased blood glucose utilization relative to normoxic conditions. However, McClelland et al. (23) reported that rats acclimatized to severe hypoxia did not increase carbohydrate utilization compared with normoxic conditions. Moreover, women acclimatized for 10 days to 4,300 m had a tendency for a lower contribution of carbohydrate oxidation to total energy expenditure during exercise, and they had a similar blood glucose disposal compared with sea level (2). In addition, Young et al. (35) suggested that, after chronic hypoxia exposure, increased mobilization and use of free fatty acids during exercise resulted in sparing of muscle glycogen. Thus there is no consensus in the literature with regard to metabolic fuel selection under hypoxic conditions. Some of the differences ob...