Nucleotide supplementation of adapted-milk formulas may be of interest for infant nutrition because nucleotides are involved in the synthesis of proteins and other macromolecules such as phospholipids, and thereby facilitate lipoprotein synthesis. To determine whether dietary nucleotides influence plasma lipoproteins in newborns, we have studied the plasma-lipoprotein concentrations and the composition of the major lipoprotein fractions during the first week of life in two groups of preterm infants fed formulas differing only in their nucleotide content. For comparison, two groups of term infants were studied under the same conditions. Lipoproteins were isolated by density ultracentrifugation, and the lipid and protein content were determined by standard methods; apolipoprotein A-I was determined immunologically. Nucleotide supplementation of formula in preterm infants increased all plasma lipoprotein concentrations. In addition, an increase in the plasma esterification rate was observed. However, total cholesterol concentrations were unchanged. The changes in lipoproteins concentrations were due mainly to an increase in apolipoprotein content. Nucleotides added to formulas affected term-infants' lipoproteins significantly less than to perterm infants. These findings suggest that dietary nucleotides may enhance the synthesis of lipoproteins during the early neonatal period, especially in preterm infants.