Mechanical unloading, an inherent characteristic of spaceflight, results in a loss of muscle mass and muscle strength. These losses threaten the integrity of space missions and crew health upon return to Earth's gravity. Nutrition-based countermeasures represent one of the few viable intervention strategies available during long-duration spaceflight. We added leucine (0.06 g • kg lean mass • meal-1; LEU) to the regular meals served 3 • d-1 to middle-aged adults (45-60 y, representative of long-duration crew members) during 14 d of horizontal bed rest (BR) and 7 d of rehabilitation. Changes in muscle mass were assessed by dual-energy X-ray absorptiometry (DEXA); strength was evaluated with standard isokinetic dynamometry. Stable isotope tracer methodology was used to quantify muscle protein synthesis pre-BR, post-BR, and post-rehabilitation. Ongoing analysis of muscle samples for measures of protein metabolism and cell signaling continues to be batched. All subjects have tolerated the supplement (leucine or placebo) well, with no complaints. Primary findings were: 1) leucine attenuated the loss of whole body lean mass during the first 7 d of BR compared to control subjects (LEU: -0.6±0.2 kg vs. CON: -1.1±0.2 kg, p<0.05) and reduced or prevented decrements in knee extensor strength (LEU: -8±3% vs. CON: -15±3%, p<0.05), ankle extensor strength (LEU: -13±5% vs. CON: -20±5%, p<0.05), and knee extensor endurance (LEU: -2±4% vs. CON: -14±3%, p<0.05) during 14 d BR; 2) LEU maintained both post-absorptive and post-prandial MPS during BR; in contrast, BR decreased post-absorptive MPS (pre-BR: 0.061% • h-1 vs. post-BR: 0.043% • h-1, p<0.05); 3) insulin area under the curve during an oral glucose tolerance test was unchanged in LEU after BR (21±8%) but elevated in CON (52±23%, p<0.05) and whole body insulin sensitivity in LEU was significantly increased above pre-BR values after 7 d rehabilitation (17±10% vs. CON: -9±9%, p<0.05).