Glucose production and oxidation were measured in ventilated preterm appropriate-for-gestational-age and small-for-gestational-age infants on the first day of life. Using a new technique of NaH13CO3 infusion followed by a [U-13C]glucose infusion, we measured glucose oxidation rates without measuring the CO2 production rate. Infants were studied at 18 +/- 4 h (mean +/- 1 SD) of life and received parenterally administered glucose only (4.2 +/- 0.5 mg.kg-1 x min-1). In 13 of 16 patients, the glucose production rate exceeded 1.0 mg.kg-1 x min-1. Infants born from mothers who had been receiving steroids antenatally had higher glucose production rates (2.3 +/- 1.1 mg.kg-1 x min-1) compared with infants from mothers who had not (1.1 +/- 0.8 mg.kg-1 x min-1, p = 0.036). The glucose oxidized (2.9 +/- 1.0 mg.kg-1 x min-1) was lower than the amount of glucose infused (p = 0.005) and was not different for appropriate-for-gestational-age and small-for-gestational-age infants. Plasma levels of glucose, insulin, glucagon, and total IGF-I were not correlated with glucose metabolism on the first day of life. Total IGF-II levels were negatively correlated with the rate of glucose appearance. We conclude that preterm infants on the first day of life receiving a glucose infusion of 4.2 mg.kg-1 x min-1 continue to produce glucose. The glucose oxidation rate is lower than the glucose infusion rate and the contribution of glucose oxidation to the total energy expenditure is limited.