The functional integrity of the gluconeogenic pathway was measured in nine term infants, four appropriate-for-gestational age (AGA), and five normoglycemic small-for-gestational age (SGA), by determination of 13C2 enrichment in blood glucose during the constant infusion of tracer [2,3]13C2]alanine between 4 and 8 h of postnatal age. Alanine flux, calculated from the steady-state blood [2,3-13C2]alanine enrichment was 16.6 +/- 1.3 (SE) (mumol.kg-1.min-1 in the AGA infants and not statistically different from the value of 15.3 +/- 0.7 mumol.kg-1.min-1 in the SGA infants. Alanine flux did not correlate with blood alanine level in either group. By 6 h of age, the earliest sampling time, there was 13C2 enrichment of blood glucose in every infant studied, indicating that the gluconeogenic pathway was functionally intact by that time and implying that it was operative sooner. At 8 h of age, 9.3 +/- 2.3% of blood glucose was derived from alanine in the AGA group and 12.9 +/- 2.4% in the SGA group, values not statistically different. These data indicate that the term human newborn has a functional gluconeogenic pathway very early in postnatal life and that intrauterine growth retardation per se does not impair maturation of the system. Furthermore, the plasma alanine level alone is a poor index of gluconeogenic carbon flow in these infants.