Chronic high-dose beta2-agonist administration has been shown to decrease skeletal muscle citrate synthase and cytochrome oxidase C activity in both endurance trained and sedentary rats, which could have deleterious effects on the oxidative capacity. Indeed, this effect has later been connected to a diminished exercise performance measured by time to exhaustion on a treadmill. Furthermore, a shift in fibre type towards a more glycolytic phenotype in response to chronic beta2-agonist administration has been demonstrated, both indicating increased dependence on anaerobic metabolism of the skeletal muscle cells. Whether or not this is also the case in humans and at therapeutic doses is unknown. The effect of chronic beta2-agonist on exercise performance and oxidative capacity was examined in a 4-week randomized, double-blinded, controlled study. Twenty one subjects was included in an active group (TER, n = 12) and a placebo group (PLA, n = 9). Throughout 4 weeks of endurance training TER received 8 x 0.5 mg terbutaline by inhalation daily. Before and after the intervention the maximal oxygen consumption (VO2-max) was measured in an incremental cycling test. Furthermore, time to exhaustion (TTE) was assessed in a relative resistance cycling test corresponding to 120% of VO2-max (120%-VO2-max-test). A significant (P≤0.01) interaction effect of group*time was observed for VO2-max. VO2-max was higher in PLA than in TER (4153±133 vs. 3990±154 ml/min) after the intervention compared with before the intervention (3904±128 vs. 3965±149 ml/min). Furthermore, a significant (P≤0.001) within-group time effect was seen in PLA on VO2-max (3904±128 vs. 4153±133 ml/min), whereas the VO2-max remained similar for TER (3965±149 vs. 3990±154 ml/min). Also, during the VO2-max-test the incremental peak power output (iPPO) was increased by 19±13W (P≤0.01) and 38±15W (P≤0.001) with the intervention in TER and PLA resulting a significant (P≤0.05) interaction effect (20±19W). Lastly, the results from the 120%-VO2-max-test revealed a significant (P≤0.05) interaction on group*time on TTE, where TTE was greater in TER than in PLA after the intervention (165,9±21 vs. 131,4±18 s) than before the intervention (127,8±17 vs. 146,1±19 ml/min). This is accompanied by a significant (P≤0.05) within-group time effect in TER (127,8±17 vs. 165,9±21 ml/min). We conclude that therapeutic doses of inhaled terbutaline blunts the endurance training-induced increase in VO2-max. Furthermore, the increase in iPPO in TER unaccompanied by a corresponding increase in VO2-max points towards an increased anaerobic energy contribution. Also, this conclusion is supported by the 120%-VO2-max-test, which shows an increased TTE in TER. Overall, results indicate that the muscle cells decreases its oxidative capacity while increasing its anaerobic energy contribution going towards a more glycolytic phenotype.