Short-term (3 to 4 hours) infusion of branched-chain amino acids (BCAA) has been shown to suppress muscle protein breakdown. Whether these effects are sustained with chronic elevations of BCAA is not known. In the present study, we examined the effect of an overnight (16-hour) systemic BCAA infusion on whole-body and skeletal muscle amino acid metabolism, as assessed by simultaneously measured 3H-phenylalanine and 14C-leucine kinetics in eight normal volunteers; 10 overnight-fasted subjects studied during a 4-hour saline infusion served as controls. Overnight BCAA infusion increased plasma BCAA concentrations by fivefold to eightfold, and this was associated with a 20% to 60% decline in arterial concentrations of other amino acids. For Phe, this decline was mediated by a reduction in the systemic rate of appearance ([Ra] 0.38 +/- 0.03 v 0.60 +/- 0.01 mumol/kg/min for BCAA and saline, respectively, P < .001). Endogenous Leu Ra, calculated more indirectly as the difference between the total Leu Ra and the unlabeled Leu infusion rate, did not differ between groups. In the forearm, overnight BCAA infusion resulted in a diminished net release of Phe (-3 +/- 2 v -18 +/- 4 [saline] nmol/min/100 mL, P < .02), and BCAA balance became markedly positive (751 +/- 93 v -75 +/- 30, P < .001). The diminished net forearm Phe release was accounted for by a decrease in local Phe Ra (P < .02). As with the systemic endogenous Leu Ra, forearm Leu Ra was not reproducibly affected by infused BCAA.(ABSTRACT TRUNCATED AT 250 WORDS)