Skeletal muscle grows at a very rapid rate in the neonatal pig, due in part to an enhanced sensitivity of protein synthesis to the postprandial rise in amino acids. An increase in leucine alone stimulates protein synthesis in skeletal muscle of the neonatal pig; however, the effect of isoleucine and valine has not been investigated in this experimental model. The left ventricular wall of the heart grows faster than the right ventricular wall during the first 10 days of postnatal life in the pig. Therefore, the effects of individual BCAA on protein synthesis in individual skeletal muscles and in the left and right ventricular walls were examined. Fasted pigs were infused with 0 or 400 micromol x kg(-1) x h(-1) leucine, isoleucine, or valine to raise individual BCAA to fed levels. Fractional rates of protein synthesis and indexes of translation initiation were measured after 60 min. Infusion of leucine increased (P < 0.05) phosphorylation of eukaryotic initiation factor (eIF)4E-binding protein-1 and increased (P < 0.05) the amount and phosphorylation of eIF4G associated with eIF4E in longissimus dorsi and masseter muscles and in both ventricular walls. Leucine increased (P < 0.05) the phosphorylation of ribosomal protein (rp)S6 kinase and rpS6 in longissimus dorsi and masseter but not in either ventricular wall. Leucine stimulated (P < 0.05) protein synthesis in longissimus dorsi, masseter, and the left ventricular wall. Isoleucine and valine did not increase translation initiation factor activation or protein synthesis rates in skeletal or cardiac muscles. The results suggest that the postprandial rise in leucine, but not isoleucine or valine, acts as a nutrient signal to stimulate protein synthesis in cardiac and skeletal muscles of neonates by increasing eIF4E availability for eIF4F complex assembly.