To determine whether glutamine can stimulate human muscle glycogen synthesis, we studied in groups of six subjects the effect after exercise of infusion of glutamine, alanine+glycine, or saline. The subjects cycled for 90 min at 70-140% maximal oxygen consumption to deplete muscle glycogen; then primed constant infusions of glutamine (30 mg/kg; 50 mg.kg-1.h-1) or an isonitrogenous, isoenergetic mixture of alanine+glycine or NaCl (0.9%) were administered. Muscle glutamine remained constant during saline infusion, decreased 18% during alanine+glycine infusion (P < 0.001), but rose 16% during glutamine infusion (P < 0.001). By 2 h after exercise, muscle glycogen concentration had increased more in the glutamine-infused group than in the saline or alanine+glycine controls (+2.8 +/- 0.6, +0.8 +/- 0.4, and +0.9 +/- 0.4 mumol/g wet wt, respectively, P < 0.05, glutamine vs. saline or alanine+glycine). Labeling of glycogen by tracer [U-13C]glucose was similar in glutamine and saline groups, suggesting no effect of glutamine on the fractional rate of blood glucose incorporation into glycogen. The results suggest that, after exercise, increased availability of glutamine promotes muscle glycogen accumulation by mechanisms possibly including diversion of glutamine carbon to glycogen.