Skeletal muscle in the neonate grows at a rapid rate due in part to an enhanced sensitivity to the postprandial rise in amino acids, particularly leucine. To elucidate the molecular mechanism by which leucine stimulates protein synthesis in neonatal muscle, overnight fasted 7-day-old piglets were treated with rapamycin (an inhibitor of mammalian target of rapamycin complex 1/mTORC1) for 1 h and then infused with leucine for 1 h. Fractional rates of protein synthesis and activation of signaling components that lead to mRNA translation were determined in skeletal muscle. Rapamycin completely blocked leucine-induced muscle protein synthesis. Rapamycin markedly reduced raptor-mTOR association, an indicator of mTORC1 activation. Rapamycin blocked the leucine-induced phosphorylation of mTOR, S6K1, and 4EBP1 and formation of the eIF4E•eIF4G complex and increased eIF4E•4EBP1 complex abundance. Rapamycin had no effect on the association of mTOR with rictor, a crucial component for mTORC2 activation, or GL, a component of mTORC1 and mTORC2 complexes. Neither leucine nor rapamycin affected the phosphorylation of AMPK, PKB, or TCS2, signaling components that reside upstream of mTOR. eEF2 phosphorylation was not affected by leucine or rapamycin, although current dogma indicates that eEF2 phosphorylation is mTOR-dependent. Taken together, these in vivo data suggest that leucine stimulates muscle protein synthesis in neonates by enhancing mTORC1 activation and its downstream effectors.