We have determined the effect of unlabeled glucose infusions, with and without added insulin, on glucose metabolism in normal male volunteers by means of the simultaneous primed-constant infusion of 6-3 H and U-13 C-glucose. Glucose kinetics were measured after 90 min of infusion. When steady state had been reached, endogenous glucose production (2.53±. 058 mg/kg· min, X±SEM) was suppressed at all rates of exogenous glucose tested (1, 2, and 4 mg/kg· min). The absolute degree of suppression was most marked (75%) at the highest rate of infusion, but the greatest degree of suppression, relative to infusion rate, was at the lowest infusion rate. The control of plasma glucose concentration during the glucose infusion was achieved primarily through regulation of endogenous Ra. The rate of uptake of glucose only increased during the 4 mg/kg· min infusion, even though there were significant elevations in the plasma glucose and insulin concentrations during the 2 mg/kg· min infusion as well. The glucose clearance rate increased only when sufficient insulin was infused with the 4 mg/kg· min glucose infusion to control the hyperglycemia that developed if no insulin was administered. Approximately 43% of the infused glucose was directly oxidized when the infusion rate was 1 or 2 mg/kg· min. That value fell to 32% when the infusion rate was increased to 4 mg/kg· min, regardless of whether insulin was infused or not.