We have used the simultaneous primed-constant infusion of 6-3H-glucose and U-14C-lactate to investigate the effect of an exogenous glucose infusion (55 μmole/kg·min) on glucose and lactate metabolism in normal and burned guinea pigs. Before the unlabeled glucose infusion, glucose turnover was higher in the burned animals than in the controls, but lactate turnover was similar. During the unlabeled glucose infusion, lactate production increased in both control (73%) and burned animals (104%), yet arterial lactate concentration did not rise in either group. The ability of tissue uptake of lactate to keep pace with increased lactate production appeared to be related to an enhancement of lactate oxidation. When a two-pool model was used to calculate glucose-lactate interrelationships, it was concluded that during the glucose infusion Cori cycle flux (glucose to lactate to glucose) was higher in burned animals than in controls. Also, the primary route of oxidation of infused glucose in controls and particularly in burned animals appeared to be through conversion to lactate and subsequent oxidation of lactate.