We have used the simultaneous primed-constant infusion of 6-³H- and U-¹³C-glucose to investigate glucose metabolism in 15 severely burned patients. Although the mean basal insulin level was significantly elevated in burn patients, the basal rate of glucose production was significantly higher (p < 0.01) than the average value for normal volunteers. The mean basal rate of glucose uptake and clearance were also both elevated in burn patients, but a decreased percentage of uptake was completely oxidized directly to CO₂. Rather, there was an increased rate of recycling of glucose carbons for reincorporation into glucose. Basal plasma concentrations of glucagon, catecholamines and cortisol were elevated in the burn patients, but no individual hormone or combination of hormone concentrations was correlated with any parameter of glucose metabolism. An exogenous glucose infusion caused an exaggerated insulin response in the burn patients. The extent of suppression of glucose production was comparable in burn patients and controls, but the high peripheral insulin concentration in the burn patients was not associated with a corresponding increase in the glucose clearance rate. Normoglycemia could be maintained during glucose infusion at 4 mg/kg · min if insulin was simultaneously infused, but approximately five times as much exogenous insulin was required in burn patients than in controls. We conclude that the burn patients had a decreased responsiveness to the action of insulin both at the liver and peripherally. Glucose production was high for the prevailing plasma insulin concentration, and high peripheral concentrations of insulin did not stimulate glucose clearance as anticipated from control studies.