The neonatal serum lipid transport system was monitored in the 1st month of life to determine the impact of oral feeding (breast versus formula). Lipid and apolipoprotein levels were measured in the serum of normal newborn infants collected at birth, 3, 14, and 28 days of age. Fatty acid and neutral lipid studies were determined by gas-liquid chromatography and apolipoprotein levels were done by electroimmunoassay. Following collection of data, the results were divided into two groups corresponding to breast-fed (BF) or formula-fed (FF) infants. Only triacylglycerols at 3 days of age were significantly higher (p<0.04) in FF infant serum when compared to BF levels. Unesterified cholesterol levels in both groups were similar at all intervals, the cholesterol esters were higher at 14 and 28 days in BF infants. ApoA-I and ApoB levels were higher at 3 days in FF, but ApoC-HI levels were the same. At all other sampling times, no discernible differences in these parameters were found between BF and FF. For the infants as a group, changes in levels with increasing age were similar for both ApoA-I and cholesterol esters, as was the case for ApoB and triacylglycerols. However, numerous differences between BF and FF were seen in molecular forms of triacylglycerols and cholesterol esters, reflecting the dietary fatty acid differences between breast milk and formula. Analyses of the fatty acid content of these two diets demonstrated that human breast milk contained twice as much palmitic and oleic acid but only one half the linoleic acid of formula. In summary, little difference in serum lipid classes and apolipoprotein levels were found between BF and FF during the first 4 wk of life. However, striking differences in the molecular forms of both triglycerides and cholesterol esters between the two groups reflected the differences in the fatty acid composition of human milk and formula.