Very low birth weight infants demonstrate significant reductions in red blood cell membrane docosahexaenoic acid (DHA, 22:6n-3) following delivery unless fed human milk. The purpose of the present study was to determine if a dietary source of DHA (MaxEPA, R. P. Scherer Corporation, Troy, MI) could prevent the decline in red blood cell phospholipid DHA in very low birth weight infants whose enteral feeding consisted of a preterm formula without DHA. Longitudinal data were obtained on membrane phospholipid DHA in both un supplemented and MaxEPA-supplemented infants by a combination of thin layer and gas chromatography. These infants (n=39) ranged in age from 10 to 53 days at enrollment (0 time). At enrollment, phospholipid DHA and arachidonic acid (20:4n-6) were inversely correlated with age in days. During the study, mean red blood cell phospholipid DHA declined without supplementary DHA as determined by biweekly measurement, but infants supplemented with MaxEPA maintained the same weight percent of phospholipid (phosphatidylethanolanine, phosphatidylcholine, and phospharidylserine) DHA as at enrollment. The pattern of red blood cell phospholipid fatty acids in supplemented infants was similar to that reported for preterm infants fed human milk. (Pediatr Res 21: 507-510,1987)