Step-reduction (SR) in older adults results in muscle atrophy and an attenuated rise in postprandial muscle protein synthesis (MPS): anabolic resistance. Knowing that resistance exercise (RT) can enhance MPS, we examined whether RT could enhance MPS following 2 weeks of SR. In addition, as we postulated that SR may impair feeding-induced vasodilation limiting nutrient delivery to muscle, we also examined whether citrulline (CIT), as an arginine and nitric oxide precursor, could attenuate muscle anabolic resistance accompanying SR. We used a unilateral leg model to compare older subjects' who had undergone SR to a loaded condition of SR plus RT (SR + RT). Thirty older men (70 ± 1 years) underwent 14 days of SR (<1500 steps/day) with supplementation of either 5 g/day CIT or glycine placebo. Throughout SR, subjects performed unilateral low-load RT thrice weekly. We assessed muscle protein synthesis in the postabsorptive and postprandial state (20 g whey isolate plus 15 g glycine or as micellar-whey with 5 g CIT or 15 g glycine, n = 10/group). As MPS was similar after ingestion of either whey isolate, micellar-whey, or micellar-whey + CIT data related to different dietary groups were collapsed to compare SR and SR + RT legs. Subjects' daily steps were reduced by 80 ± 2% during SR (P < 0.001) compared with baseline. Leg fat-free mass decreased with SR (-124 ± 61 g) and increased in the SR + RT (+126 ± 68 g; P = 0.003). Myofibrillar FSR was lower (P < 0.0001) in the SR as compared with the SR + RT leg in the postabsorptive (0.026 ± 0.001%/h vs. 0.045 ± 0.001%/h) and postprandial states (0.055 ± 0.002%/h vs. 0.115 ± 0.003%/h). We conclude that low-load RT, but not supplementation with CIT, can attenuate the deleterious effects of SR in aging muscle.