It has been hypothesized that myostatin, a newly identified member of the transforming growth factor-beta (TGF-beta) family of proteins, acts as a negative regulator of skeletal muscle growth. Because bed rest induced muscle atrophy results from a decreased rate of muscle protein synthesis, we hypothesized that circulating levels of myostatin would be increased following prolonged bed rest. Twelve men (age, 35.8 +/- 4.6 yr; height, 175.7 +/- 2.3 cm; weight, 74.8 +/- 3.5 kg; mean +/- SE) were confined to bed for 25 days at 6 degrees head-down tilt while receiving triiodothyronine (T3; 50 micrograms/day) to accelerate protein loss. Total lean body and appendicular skeletal muscle mass were determined by dual energy x-ray absorptiometry (DEXA) before and after the bed rest period. Plasma myostatin-immunoreactive protein was measured in blood samples obtained after an overnight fast 5 days prior to, and on the 25th day of bed rest. Lean body mass decreased an average 2.2 kg (p < 0.0001). Appendicular skeletal muscle accounted for a majority of the lean body mass loss. On day 25 of bed rest, plasma myostatin-immunoreactive protein was 12% higher (p = 0.01) than measured at baseline. These data support the idea that myostatin regulates muscle growth in humans and that it may be a novel target for interventions aiming to reduce space flight induced muscle atrophy.