In vitro, insulin has been shown to increase skeletal muscle (SM) protein synthesis and decrease SM protein breakdown. Whether these same effects are found in vivo in man is less clear. The study of the effect of hyperinsulinemia (INS) on SM protein turnover (SMPT) is complicated by hypoaminoacidemia, which can obviate the true effect of insulin on SMPT. To prevent this, we studied the effect of INS on SMPT in the human forearm with amino acid (AA) infusion to ensure adequate substrate for full evaluation of insulin's effect. Twelve healthy volunteers (aged 53 ± 3 years) were studied. Steady-state AA kinetics were measured across the foream after a systemic 2-hour primed continuous infusion of 3H-phenylalanine (3H-Phe) and 14C-leucine (14C-Leu) in the postabsorptive (PA) state and in response to systemic INS (71 ± 5 μU/mL). AAs were infused during INS as 10% Travasol (Travenol Laboratories, Deerfield, IL) at .011 mL/kg/min to maintain PA branched-chain AA (BCAA) levels, known regulators of SMPT, and to mildly elevate total AA levels. The negative PA net balance of both Phe and total Leu carbons (LeuC) became positive with INS + AA infusion (Phe from -16 ± 2 to 12 ± 3 nmol/min 100 g [P < .01]; LeuC from -26 ± 6 to 24 ± 7 nmol/min 100 g [P < .01]). The rate of disposal (Rd) of Phe into SM, an index of protein synthesis, increased from 31 ± 5 nmol/min 100 g postabsorptively to 52 ± 7 nmol/min 100 g with INS + AA (P < .01), while the LeuC Rd increased from 82 ± 16 to 86 ± 18 nmol/min 100 g (P = .85). The rate of appearance (Ra) of phe from SM, an index of protein breakdown, decreased from 48 ± 6 nmol/min 100 g postabsorptively to 40 ± 5 nmol/min 100 g with INS + AA (P = .06), while the LeuC Ra decreased from 107 ± 18 to 62 ± 14 nmol/min 100 g (P < .03). These data suggest that the anabolic effect of insulin across the human forearm, in the presence of mildly elevated arterial AA levels, is to increase SM protein synthesis and decrease SM protein breakdown. © 1994.