We determined the effect of supplementing milk formula with nucleotides on plasma lipoproteins in small-for-gestational-age infants: 21 infants were fed a nucleotide-supplemented formula and 20 infants were fed the same nucleotide-free formula. On days 0, 3 and 7 after birth, major plasma lipoprotein fractions were analyzed for apolipoprotein and lipid composition. Compared with the control group, the group receiving nucleotides had increased total apoprotein concentrations in all lipoproteins as well as increased apo A-I in high-density lipoproteins and very low-density lipoproteins, and apo B-100 in very low-density lipoproteins and low-density lipoproteins. Very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol and very low-density lipoprotein triglycerides increased in parallel to the changes in apoproteins. The cholesterol ester to unesterified cholesterol ratio was increased in low-density lipoproteins and, particularly, in high-density lipoproteins. These data support the hypothesis that lipoprotein metabolism in small-for-gestational-age infants is affected by dietary nucleotide supplementation, enhancing lipoprotein synthesis or secretion. Cholesterol esterification capacity paralleled the apo A-I increase, in agreement with the cofactor role of apo A-I on lecithin: cholesterol acyltransferase.