FA are known to modulate immune function in conditions such as arthritis and lupus erythematosus. The effects of arachidonic (AA) and oleic acids (OA) on function and pleiotropic gene expression of Raji cells were investigated. The following parameters were evaluated: cytotoxicity as assessed by loss of membrane integrity and DNA fragmentation; proliferation as measured by [14C]thymidine incorporation; production of interleukin (IL)-10, interferon (INF)-gamma, and tumor necrosis factor (TNF)-alpha; and expression of pleiotropic genes by a macroarray technique (83 genes in total). AA was more toxic to Raji cells than OA. Both FA promoted an increase in Raji cell proliferation at 75 microM, whereas OA at high concentrations (200 microM) decreased proliferation. AA reduced the production of IL-10, TNF-alpha, and INF-gamma. On the other hand, OA provoked an increase of INF-gamma production but did not affect the production of IL-10 and TNF-alpha. The proportions of genes with altered expression were 27% for AA and 35% for OA. The FA affected the expression of genes clustered as: cytokines, signal transduction pathways, transcription factors, cell cycle, defense and repair, apoptosis, DNA synthesis, cell adhesion, cytoskeleton, and hormone receptors. The most remarkable changes were observed in the genes of signal transduction pathways. These results led us to conclude that the effect of these FA on B-lymphocytes includes regulation of gene expression. Thus, diets enriched with fat containing OA or AA may affect B lymphocyte function in vivo.