Human milk contains relatively high amounts of acid-soluble nucleotides, mainly CMP, AMP, UMP, IMP, and UDP sugars, and lacks orotate. On the contrary, cow's milk and adapted formulas contain high amounts of orotate and very low amounts of CMP and AMP. Nucleotides may be modulators of metabolic functions in gut and liver. To evaluate the possible role of dietary nucleotides in newborn fatty acid metabolism, we studied the polyunsaturated fatty acid (PUFA) composition of erythrocyte membrane phospholipids in 58 term infants at 30 days of age. Twenty of them were fed human milk (HM), 19 an adapted formula (MF), and 19 with the same formula supplemented with nucleotides (NMF) in an amount similar to that present in HM. Relative content of omega 6 and 3 PUFA greater than 18 carbon atoms was significantly reduced especially in phosphatidylethanolamine and phosphatidylserine for infants fed regular MF compared with those fed HM or NMF. Unsaturation index of red blood cell phospholipids showed a similar effect. These results suggest that dietary nucleotides play a role in the in vivo desaturation and elongation of essential fatty acids to long chain PUFA during early life for the human newborn.