We have previously shown that diets enriched with (n-3) fatty acids reduced the delayed-type hypersensitivity (DTH) skin reaction to keyhole limpet haemocyanin (KLH) in geriatric-Beagles. Although the amount of ��-tocopheryl acetate in diets of the previous study exceeded requirements, plasma ��-tocopherol concentration was significantly lower in dogs fed the high (n-3) fatty acid diets. There are several reasons that could explain the decreased DTH response. Some of these include decreased cytokine production, specifically, interleukin (IL) IL-1��, tumor necrosis factor (TNF) and IL-6 by mononuclear cells. Furthermore, the reduced DTH response could be attributed to increased levels of lipid peroxides or changes in plasma ��-tocopherol levels. In this study we examined the effects of feeding 32 healthy, female, geriatric-Beagles diets containing (n-6) to (n-3) fatty acid ratios of 37:1 and 1.7:1, while varying the content of ��-tocopheryl acetate, [high (447 ug/g), med (101 ug/g) and low (17 ug/g)] for 82 days on the DTH reaction. Consumption of the 1.7:1 fatty acid diets significantly increased the total content of (n-3) fatty acids in plasma compared to the 37:1 fatty acid diets (17.00 and 2.02 wt %, respectively). There was a significant interaction between the (n-6) and (n-3) fatty acid ratio and the concentration of ��-tocopheryl acetate in the diet on the plasma concentration of ��-tocoopherol. The concentration of ��-tocopheryl acetate in plasma of dogs fed the 1.7:1 fatty acid diets was 17.3, 25.4, and 35.4 ug/ml, respectively, for the low, med and high ��-tocopheryl acetate containing diets, and in dogs fed the 37:1 fatty acids diets was 20.8, 34.9, 52.4 ug/ml, respectively. Consumption of the 1.7:1 fatty acid diets with either low or high ��-tocopheryl acetate showed no differences in DTH response from each other or from dogs consuming the 37.1:1 fatty acid diets. When the dietary ��-tocopheryl acetate concentration was moderate, a significant suppression of the DTH response occurred at 48, 72, and 96 hr in dogs consuming the 1.7:1 fatty acid diet. These data suggest that an interaction exits between dietary (n-3) fatty acid content and ��-tocopheryl acetate on the immune response as measured by the DTH test. / Graduation date: 2000