Transforming growth factor-β (TGF-β) superfamily consists of more than thirty members that are TGF-βs, bone morphogenic proteins (BMPs), growth differentiation factor (GDFs), activins and others1 . Among them, GDFs mainly regulates cartilage and skeletal development, and one of the GDF proteins, GDF-8, which is designated as myostatin, functions as a negative regulator of skeletal muscle volume. In the previous studies, inactivation of the myostatin gene in knockout mice significantly increased muscle volume up to 2-fold and systemic myostatin-overexpression induced cachexia in adult mice2 . It is also known that the activity of myostatin is physiologically regulated in several ways. One of which is the inactivation by myostatin prodomain. Lee, et al., reported that a cleaved N-terminal prodmain sequence of myostatin precursor interacted with the mature myostatin at the C-terminal part3 . Hence, in the present study, we have focused on the N-terminal region of mouse prodomain sequence to discover a short peptide that selectively binds to human myostain, resulting in the inhibition of myostatin function. Using a reporter assay with pCAGA12-luc, which is activated via the intracellular Smad signaling pathway lying downstream of the myostatin receptor, we screened synthetic peptide fragments and found a selective myostatin inhibitory peptide (24 AA, named as “mighty peptide 1”) with an IC50 value of 4.1 μM. Phosphorylation of Smad2 protein was also inhibited by the treatment with the peptide 1. Moreover, intramuscular administration of 1 in the groin of mice notably increased the femoral muscle volume. Therefore, peptide 1 would be a significant starting point for the development of more potent inhibitors, which may contribute to the treatment of muscular diseases in a near future.