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' as compared to 'high-volume low-intensity' exercise training was evaluated. A group of sedentary premenopausal women aged 45±6 years (±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 non-training control group (CON, n=20), the training groups completed three workouts per week for 15 weeks. Resting muscle biopsies were obtained from m. vastus lateralis and m. deltoideus before and after the intervention. After the training intervention, a larger (P<0.05) increase existed in m. deltoideus of the HIS group compared to m. vastus lateralis 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 m. deltoideus citrate synthase maximal activity, citrate synthase protein expression, and muscle glycogen content. In conclusion, m. deltoideus has a higher adaptive potential than m. vastus lateralis 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 m. deltoideus.