Comparative effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) acid on Jurkat T cells were investigated. The following parameters were evaluated: concanavalin A (Con A) induced proliferation, production of interleukin-2 (IL-2), IL-4, IL-10, and interferon-gamma (INF-gamma), and expression of pleiotropic genes by macroarray technique (83 genes in total). DHA inhibiting effect on Con A-induced proliferation was more pronounced than that of EPA. The decrease in IL-2 and INF-gamma production was observed for both fatty acids, whereas the production of IL-10 was decreased by EPA only. The expression of a significant proportion of genes was altered by the fatty acids; 30% for DHA (25 genes) and 26.5% for EPA (22 genes). DHA and EPA markedly affected the expression of genes clustered as cytokines and related receptors, signal transduction pathways, transcription factors, cell cycle, defense and repair, apoptosis, DNA synthesis, cell adhesion, cytoskeleton, and hormone receptors. Therefore, the effect of fatty acids on T-lymphocyte function involves regulation of expression of important genes. Marked differences were observed between the effects of EPA and DHA, indicating that it is an over-simplification to generalize the effects of n-3 fatty acids.