Total carbohydrate oxidation, plasma glucose oxidation, and glucose carbon recycling were measured in 11 fasting newborns using a constant infusion of D-[U-13C]glucose combined with respiratory calorimetry. The "true" rate of glucose appearance (Ra) was quantified from the enrichment of the nonrecycling tracer species (m + 6), while the "apparent" rate of glucose appearance was quantified from the enrichment of glucose C - 1. The plasma glucose concentration remained constant at approximately 50 mg/dl (2.8 mM) throughout the study. The true rate of glucose production was 5.02 +/- 0.41 mg X kg-1 X min-1, (means +/- SD). Glucose was oxidized at a rate of 2.67 +/- 0.34 mg X kg-1 X min-1 and represented 53% of the glucose turnover. Recycling of glucose carbon represented 36% of the glucose production rate, or 1.87 +/- 0.74 mg X kg-1 X min-1. The oxidation of plasma glucose provided 15.8 +/- 2.0 kcal X kg-1 X day-1, whereas total carbohydrate oxidation (measured by respiratory calorimetry) provided 19.9 +/- 6.6 kcal X kg X day. The data indicate that 1) recycling of glucose carbon accounts for about one-third of glucose production, demonstrating active gluconeogenesis in the fasting newborn; 2) the oxidation of plasma glucose represents only 80% of total carbohydrate oxidation, the remaining 20% possibly representing the local oxidation of tissue glycogen stores; and 3) as the measured rate of glucose oxidation will be insufficient to supply the entire calculated cerebral metabolic requirements, these data suggest that fuels in addition to glucose may be important for cerebral metabolism in the fasting human newborn.