Rats were fed for 6 weeks on a low fat (LF) diet or on high fat diets containing safflower oil [SO; rich in n-6 polyunsaturated fatty acids (PUFAs)] or fish oil (FO; rich in n-3 PUFAs), Lymph-borne dendritic cells (L-DC) were isolated after cannulation of the thoracic duct and were used as antigen [keyhole limpet hemocyanin (KLH)] -presenting cells in an ex vivo assay that used KLH-sensitized spleen lymphocytes as the responder cells, FO feeding significantly diminished the antigen presentation activity of L-DC compared with L-DC from rats fed each of the other diets, The antigen presentation activity of L-DC from rats fed the SO diet was greater than that of L-DC from rats fed the LF diet, Feeding the FO diet significantly reduced both the proportion of CD2-positive L-DC and the level of CD2 expression on L-IDC compared with feeding each of the other diets; the proportions of L-DC staining positive for CD40, CD18, CD54, CD11a, and MHC II were unaffected by diet, However, FO feeding reduced the level of expression of CD18, CD11a, MHC II, and CD54 on L-DC compared with feeding the other two diets; the level of expression of CD40 was unaffected by diet, This is the first study to report effects of dietary fatty acids on dendritic cells. The suppressive effect of FO feeding may account for some of the beneficial effects of n-3 polyunsaturated fatty acids observed in clinical settings, suck as prolonged survival of grafts and diminished chronic inflammatory responses, However, such an effect may also be detrimental because host defense toward bacterial and other antigens could be compromised.