Objective: To investigate if supplementation of preterm infant formula with a high docosahexaenoic acid/eicosapentaenoic acid (DHA/EPA) ratio together with a-linolenic acid (ALA) was able to maintain plasma and red blood cell DHA levels similar to that obtained with breast milk feeding without altering n-6 fatty acid status. Design and subjects: Preterm infants of mothers who elected not to breast feed (n ¼ 13) were assigned to ALA-and DHAenriched formula (DHA group: DHA/EPA ¼ 5/l). Infants fed breast milk (n ¼ 25) constituted a reference group (BM group). Anthropometric and fatty acid parameters (plasma phospholipids, cholesterol esters, triglycerides and red blood cell phosphatidylethanolamine, PL, CE, TG, RBC-PE, respectively) were obtained after 2 days (D2) and 15 days (D15) of enteral feeding and at the 37th week (W37) of post-conception age and 1 month later (W37+30) in the DHA group. Mean DHA intake ranged between 16.571.6 and 17.972.9 mg/kg/day between D2 and W37+30. Results: At W37, infant weights, heights, and head circumferences were similar in DHA and BM groups. PL DHA was maintained in the DHA group at the same level as in the BM group and the same for DHA in PE at W37. In RBC-PE and at W37, AA status was the same in both groups. In PL, AA levels remained very stable throughout the study; however, in the DHA group AA levels in PL remained in the range observed with standard formulas. Conclusion: The combined 18:3 n-3 and DHA supplementation of infant formula with DHA/EPA ratio 5/l is compatible with growth and n-3 fatty acid metabolism similar to that of preterm infants fed human milk.