To evaluate the mechanism(s) of the observed increase in plasma glucose concentration following the administration of an intravenous fat emulsion to the neonate, we measured glucose kinetics in eight low-birth-weight neonates by the prime constant rate infusion technique with D-[6,6-2H2]glucose at a rate of 0.22 +/- 0.01 mumol.kg-1 x min-1 (39.4 +/- 1.3 micrograms.kg-1 x min-1) while the neonates received 32 +/- 5 mumol.kg-1 x min-1 glucose (6.3 +/- 1.1 mg.kg-1 x min-1) plus an amino acid mixture (parenteral alimentation) alone and in combination with an intravenous fat emulsion (Intralipid). Following the latter combination, there were significant increases in plasma glucose concentration [4.07 +/- 0.11 (73 +/- 2 mg/dl) to 5.00 +/- 0.22 mmol/l (90 +/- 4 mg/dl); P < 0.01] and in plasma insulin concentration [72 +/- 14 (10 +/- 2 microU/ml) to 172 +/- 36 pmol/l (24 +/- 5 microU/ml); P < 0.05]. The parenteral alimentation and intravenous fat effusion combination did not affect the glucose production rate: 0.15 +/- 0.05 mumol.kg-1 x min-1 (0.03 +/- 0.01 mg.kg-1 x min-1) during the parenteral alimentation alone and 0.16 +/- 0.05 mumol.kg-1 x min-1 (0.03 +/- 0.01 mg.kg-1 x min-1) when parenteral alimentation was combined with an intravenous fat emulsion. We conclude that the increased plasma glucose concentration seen in association with administration of parenteral alimentation combined with an intravenous fat emulsion to the premature neonate is not due to enhanced glucose production but could be the result of alterations in glucose utilization.