The present study concerns the effects of 21 days of sustained recumbence (bedrest) and hypoxia alone and in combination on skeletal muscle microRNA expression. 14 male subjects participated in 3 experimental campaigns in a counterbalanced fashion: normoxic bedrest (NBR) hypoxic bedrest (HBR) and hypoxic ambulatory confinement (HAMB) both hypoxic conditions with FO2 = 0.141 and PIO2 = 90 xc2 xb1 0.4 mmHg equivalent to an altitude of xe2 x89 x88 4000 m). Each intervention (bedrest or ambulatory confinement) lasted 21 days and the interventions were separated by a 4-month wash-out/recovery period. The order in which each subject undertook the interventions is denoted Intervention_order Throughout both bedrest interventions each subject remained in a horizontal position at all times. He was allowed one pillow for the head and to occasionally lean on an elbow while eating or being transferred to a gurney. Muscular exercise was prohibited. During the HAMB confinement each subject was allowed to move freely within the hypoxic area. To mimic a normal level of physical activity subjects performed 30 minutes of low-to-moderate-intensity exercise twice daily. Muscle samples from Vastus lateralis.