Docosahexaenoic acid (DHA), a crucial nervous system n-3 PUFA, may be obtained in the diet or synthesized in vivo from dietary a-linolenic acid (LNA). We addressed whether DHA synthesis is regulated by the availability of dietary DHA in artificially reared rat pups, during p8 to p28 development. Over 20 days, one group of rat pups was continuously fed deuterium-labeled LNA (d5-LNA) and no other n-3 PUFA (d5-LNA diet), and a second group of rat pups was fed a d5-LNA diet with unlabeled DHA (d5-LNA 1 DHA diet). The rat pups were then euthanized, and the total amount of deuterium-labeled docosahexaenoic acid (d5-DHA) (synthesized DHA) as well as other n-3 fatty acids present in various body tissues, was quantified. In the d5-LNA 1 DHA group, the presence of dietary DHA led to a marked decrease (3-to 5-fold) in the total amount of d5-DHA that accumulated in all tissues that we examined, except in adipose. Overall, DHA accretion from d5-DHA was generally diminished by availability of dietary preformed DHA, inasmuch as this was found to be the predominant source of tissue DHA. When preformed DHA was unavailable, d5-DHA and unlabeled DHA were preferentially accreted in some tissues along with a net loss of unlabeled DHA from other organs.-DeMar, Jr., J. C., C. DiMartino, A. W. Baca, W. Lefkowitz, and N. Salem, Jr. Effect of dietary docosahexaenoic acid on biosynthesis of docosahexaenoic acid from alpha-linolenic acid in young rats. J. Lipid Res. 2008Res. . 49: 1963Res. -1980 Supplementary key words essential fatty acids • lipid metabolism • early development • infant formula composition Docosahexaenoic acid (DHA; 22:6n-3) is an n-3 PUFA that is particularly enriched in the phospholipids of cells constituting the mammalian nervous system (1, 2). Functionally, DHA enhances membrane elasticity and molecular motion and thus promotes signal transduction via enhanced protein/receptor interactions (3-6). DHA is also the activating ligand for multiple transcriptional factors that control the expression of enzymes involved in fatty acid synthesis and b-oxidation (7). DHA may be directly obtained in the diet, as preformed DHA, or synthesized in vivo from other common dietary n-3 PUFAs such as a-linolenic acid (LNA, 18:3n-3), eicosapentaenoic acid (EPA, 20:5n-3), or docosapentaenoic acid (DPA, 22:5n-3) (8). All of these n-3 PUFAs may be converted in vivo to DHA through sequential steps of elongation, desaturation, and peroxisomal b-oxidation (9). Prolonged dietary deprivation of all n-3 PUFAs in rat pups, initiated prior to weaning, depletes up to 80% of their brain DHA (10-12). Such depletion of brain DHA in rodents leads to distinct impairments in brain function (11,(13)(14)(15)(16)(17). Piglets and monkeys also show impaired neural function when deprived of n-3 PUFA for an extended period during infancy (18,19). The essentiality of DHA for human infant nutrition in support of neuronal function has been shown by DHA supplementation, enhancing visual acuity and cognition-related test scores in human infants (20)(21)(2...