It was investigated if skeletal muscle K(+) release is linked to the degree of anaerobic energy production. Six subjects performed an incremental bicycle exercise test in normoxic and hypoxic conditions prior to and after 2 and 8 weeks of acclimatization to 4100 m. The highest workload completed by all subjects in all trials was 260 W. With acute hypoxic exposure prior to acclimatization, venous plasma [K(+)] was lower (P<0.05) in normoxia (4.9+/-0.1 mM) than hypoxia (5.2+/-0.2 mM) at 260 W, but similar at exhaustion which occurred at 400+/-9 W and 307+/-7 W (P<0.05), respectively. At the same absolute exercise intensity, leg net K(+) release was unaffected by hypoxic exposure independent of acclimatization. After 8 weeks of acclimatization no difference existed in venous plasma [K(+)] between the normoxic and hypoxic trial, neither at submaximal intensities nor at exhaustion (360+/-14 W vs. 313+/-8 W; P<0.05). At the same absolute exercise intensity, leg net K(+) release was less (P<0.001) than prior to acclimatization and reached negative values in both hypoxic and normoxic conditions after acclimatization. Moreover, the reduction in plasma volume during exercise relative to rest was higher (P<0.01) in normoxic than hypoxic conditions, irrespective of the degree of acclimatization (at 260 W prior to acclimatization: -10.0+/-0.4 % in normoxia and -4.9+/-0.8 % in hypoxia). It is concluded that leg net K(+) release is unrelated to anaerobic energy production and that acclimatization reduces leg net K(+) release during exercise.