Pre-term infants, that are not breast-fed, are deprived of vital intrauterine fat accretion during late pregnancy and must rely on formula to obtain fatty acids essential for normal development, particularly of the visual system. Preterm infants (30 wk postconception) receiving human milk were compared to infants given one of the following formulae: Formula A was a commercial preterm formula with predominantly 18:2 omega 6 (24.2%) and low (0.5%) 18:3 omega 3; Formula B was based on soy oil and contained similar 18:2 omega 6 levels (20%) and high 18:3 omega 3 (2.7%); Formula C was also a soy oil-based formula (20% 18:2, 1.4% 18:3) but was supplemented with marine oil to provide omega 3 long-chain polyunsaturated fatty acids (LCP) at a level (docosahexaenoic acid, DHA, 0.35%) equivalent to human milk. At entry (10 days of age), the fatty acid composition of plasma and red blood cell (RBC) membrane lipids of the formula groups were identical. By 36 wk postconception, the DHA content in lipids of group A was significantly reduced compared to that in the human milk and marine oil formula groups. Omega-3 LCP results were further amplified by 57 wk with compensatory increases in 22:5 omega 6 in both plasma and RBC lipids. Provision of 2.7% alpha-linolenic acid in formula group B was sufficient to maintain 22:6 omega 3 levels equivalent to those in human milk-fed infants at 36 wk but not at 57 wk. Effects on the production of thiobarbituric acid reactive substances and fragility of RBC attributable to the marine oil supplementation were negligible. The results support the essentiality of omega 3 fatty acids for preterm infants to obtain fatty acid profiles comparable to infants receiving human milk. Formula for preterm infants should be supplemented with omega 3 fatty acids including LCP.