The relationship between fatty acids in plasma and basal (B), interleukin-2-(IL-2), and interferon-alpha (IFN-alpha)-stimulated natural killer (NK) cell activity was studied in healthy elderly men aged on average 70.5 y (65-81 y). B-NK correlated significantly with the fraction of plasma fatty acids consisting of total polyunsaturated fatty acids (PUFAs), total n-6 fatty acids, and linoleic acid (r = -0.68, r = -0.62, and r = -0.52, respectively). Significant negative correlations were also found between IFN-alpha stimulated NK cells and the three groups of fatty acids and between IL-2-stimulated NK cells and PUFAs. Likewise, negative correlations between PUFAs in the diet and B-NK, IL-2 and IFN-alpha stimulated NK cell activity were found. The number of NK cells increased significantly but NK cell activity did not change after 5 wk on a diet lower in fat but higher in PUFAs than the subjects' habitual diet. It is concluded that the amount and type of dietary fatty acids influence in vitro measures of immune function in elderly men. From an immunological point of view, a high intake of n-6 PUFAs may be inadvisable.