The influence of fetal glucose and amino acid supply on the regulation of fetal plasma IGF-I levels was investigated in fetuses from starved ewes. Paired maternal and fetal blood samples were taken during an initial 2-d control period, after 48 h of maternal starvation, during a 24-h fetal infusion of glucose (n = 6) or an amino acid mixture (Synthamin 17, n = 5) with continued starvation, and after 48 h of maternal refeeding. After 48 h of starvation, maternal and fetal plasma IGF-I, insulin, and blood glucose fell significantly in both groups compared with control values (IGF-I for glucose group: maternal, -18.53 +/- 6.60; fetal, -5.23 +/- 1.81 nmol/L; amino acid group: maternal, -18.2 +/- 6.97, fetal, -5.12 +/- 1.61 nmol/L; both p < 0.05). Fetal glucose but not mixed amino acid infusion raised fetal plasma IGF-I, insulin, and blood glucose to near control values (glucose group fetal IGF-I, -1.77 +/- 1.98; amino acid group, -5.93 +/- 2.22 nmol/L; both p < 0.05). Maternal plasma IGF-I remained depressed during glucose infusion (-16.33 +/- 8.32 nmol/L), but continued to fall in the amino acid group (-21.41 +/- 8.20 nmol/L, p < 0.05). After 48 h of maternal refeeding, all values had returned to near control values for both groups (glucose group IGF-I: maternal, -5.2 +/- 3.86; fetal, 0.01 +/- 2.2; nmol/L; amino acid group: maternal, -11.66 +/- 3.2; fetal, -0.70 +/- 2.61 nmol/L). We conclude that in the ovine fetus glucose may have a more important role than amino acids in the regulation of fetal plasma IGF-I.