Serine plays an important role in intermediary metabolism as a source of one carbon pool for nucleotide biosynthesis, as a precursor for glycine and glucose, and as a contributor to cysteine biosynthesis. A unique serine-glycine cycling between the liver and the placenta has been demonstrated in the sheep fetus. We hypothesized that, because of serine's role in growth and development, significant changes in serine metabolism will occur in pregnancy with advancing gestation. The rate of appearance (R_a) of serine and its metabolism were quantified in healthy women longitudinally through pregnancy with a [2-¹⁵N¹³C]serine tracer. The contribution of serine N to urea and the rate of oxidation of serine were measured using the precursor-product relation. Plasma serine concentrations and serine R_a were lower in pregnant (P) women, in both early and late gestation, compared with nonpregnant (NP) women [plasma serine: NP, 113 ± 24.5; P early, 71.9 ± 6.2; P late, 68.5 ± 9.6 µmol/l; serine R_a: NP (n = 7), 152.9 ± 42.8; P early (n = 12), 123.7 ± 21.5; P late (n = 8), 102.8 ± 18.2 µmol · kg¹ · h¹]. Serine contributed ~6% to urea N and 15-20% to the plasma glycine pool, and oxidation of serine represented ~8% of R_a. There was no significant difference between P and NP subjects. Glucose infusion, at 3 mg · kg¹ · min¹ in P subjects, resulted in a decrease in serine R_a and an increase in oxidation. The decrease in serine turnover in pregnancy may represent a decrease in -amino nitrogen turnover related to a decreased rate of branched-chain amino acid transamination and caused by pregnancy-related hormones aimed at nitrogen conservation and accretion.