The increase in fractional rate of protein synthesis (Ks) in the skeletal muscle of growing rats during the transition from fasted to fed state has been explained by the synergistic action of a rise in plasma insulin and branched-chain amino acids (BCAA). Since growing lambs also exhibit an increase in Ks with level of feed intake, the objective of the present study was to determine if this synergistic relationship between insulin and BCAA also occurs in ruminant animals. Six 30 kg fasted (72 h) lambs (8 months of age) received each of four treatments, which were based on continuous infusion into the jugular vein for 6 h of: (1) saline (155 mmol NaCl/l); (2) a mixture of BCAA (0.778 micromol leucine, 0.640 micromol isoleucine and 0.693 micromol valine/min.kg); (3) 18.7 micromol glucose/min.kg (to induce endogenous insulin secretion); (4) co-infusion of BCAA and glucose. Within each period all animals received the same isotope of phenylalanine (Phe) as follows: (1) L-[1-13C]Phe; (2) L-phenyl-[ring 2H5]-alanine; (3) L-[15N]Phe; (4) L-[ring 2,6-3H]Phe. Blood was sampled serially during infusions to measure plasma concentrations of insulin, glucose and amino acids, and plasma free Phe isotopic activity; biopsies were taken 6 h after the beginning of infusions to determine Ks in m. longissimus dorsi and vastus muscle. Compared with control (saline-infused) lambs, Ks was increased by an average of 40% at the end of glucose infusion, but this effect was not statistically significant in either of the muscles sampled. BCAA infusion, alone or in combination with glucose, also had no significant effect on Ks compared with control sheep. Ks was approximately 60% greater for vastus muscle than for m. longissimus dorsi (P<0.01), regardless of treatment. It is concluded that there are signals other than insulin and BCAA that are responsible for the feed-induced increase in Ks in muscle of growing ruminant animals.