The hypothesis that the adaptive capacity is higher in human upper- than lower-body skeletal muscle was tested. Furthermore, the hypothesis that more pronounced adaptations in upper-body musculature can be achieved by "low-volume high-intensity" compared with "high-volume low-intensity" exercise training was evaluated. A group of sedentary premenopausal women aged 45 ± 6 yr (± SD) with expected high adaptive potential in both upper- and lower-extremity muscle groups participated. After random allocation to high-intensity swimming (HIS, n = 21), moderate-intensity swimming (MOS, n = 21), soccer (SOC, n = 21) or a nontraining control group (CON, n = 20), the training groups completed three workouts per week for 15 wk. Resting muscle biopsies were obtained from the vastus lateralis muscle and deltoideus muscle before and after the intervention. After the training intervention, a larger (P < 0.05) increase existed in deltoideus muscle of the HIS group compared with vastus lateralis muscle of the SOC group for citrate synthase maximal activity (95 ± 89 vs. 27 ± 34%), citrate synthase protein expression (100 ± 29 vs. 31 ± 44%), 3-hydroxyacyl-CoA dehydrogenase maximal activity (35 ± 43 vs. 3 ± 25%), muscle glycogen content (63 ± 76 vs. 20 ± 51%), and expression of mitochondrial complex II, III, and IV. Additionally, HIS caused higher (P < 0.05) increases than MOS in deltoideus muscle citrate synthase maximal activity, citrate synthase protein expression, and muscle glycogen content. In conclusion, the deltoideus muscle has a higher adaptive potential than the vastus lateralis muscle in sedentary women, and "high-intensity low-volume" training is a more efficient regime than "low-intensity high-volume" training for increasing the aerobic capacity of the deltoideus muscle.