Alterations in dietary FAs are reported to affect immunity via effects upon cytokine gene expression, eicosanoid synthesis and membrane physicochemical properties. The effects of maternal diet FA composition upon thymocyte subset distribution were studied in neonatal rat pups. Methods: Timed pregnant dams were fed, beginning on day 2 of gestation and throughout lactation, either chow (control) or a purified diet whose fat source (22% of cals) was corn oil (high n6) or menhaden fish oil (high n3). On day 3 of life, pups were culled to 10 per dam and were randomly cross-fostered among dams fed the same diets to minimize litter effects. Culled pup thymuses were removed for FA analysis. On day 7 of life, pups were sacrificed and thymuses removed for flow cytometric analysis of thymocyte subsets; milk samples were collected for FA analysis. Results: Length of gestation and pup weights did not differ among diet groups. The FA composition of maternal milk and pup thymuses reflected maternal diet, with a significant enrichment of n6 and n3 FAs in the corn and fish groups, respectively (FA data shown for pup thymus only). The percent of double positive immature thymocytes (CD4+CD8+) was significantly lower in the fish versus corn group, while the percent of CD4+CD8-, CD3brtCD4brt and CD3brtCD8brt thymocytes was significantly higher in the fish versus corn and chow groups.Conclusion: The FA composition of pre- and/or postnatal diet affects the FA composition of neonatal thymus, and may influence thymocyte differentiation. (Funded in part by Ross Products Division)Table