We determined whether essential amino acid and carbohydrate supplementation could offset the catabolic response to prolonged inactivity. Major outcome measures included mixed muscle fractional synthetic rate (FSR), phenylalanine net balance, lean leg mass, and leg extension strength. On d 1 and 28, vastus lateralis muscle biopsies and femoral arterio-venous blood samples were obtained during a primed constant infusion of l-[ring-(2)H(5)]phenylalanine. Net balance and FSR were calculated over 16 h, during which the control group (CON) received a nutritionally mixed meal every 5 h (0830, 1330, and 1830 h). The experimental group (EXP) also consumed 16.5 g essential amino acids and 30 g carbohydrate (1100, 1600, and 2100 h). The dietary regimen was maintained during bedrest. FSR was higher in the EXP group on d 1 (EXP, 0.099 +/- 0.008%/h; CON: 0.075 +/- 0.005%/h) and d 28 (EXP, 0.093 +/- 0.006%/h; CON, 0.055 +/- 0.007%/h). Lean leg mass was maintained throughout bedrest in the EXP group (+0.2 +/- 0.3 kg), but fell in the CON group (-0.4 +/- 0.1 kg). Strength loss was more pronounced in the CON group (EXP, -8.8 +/- 1.4 kg; CON, -17.8 +/- 4.4 kg). Essential amino acid and carbohydrate supplementation may represent a viable intervention for individuals at risk of sarcopenia due to immobility or prolonged bedrest.