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Increased dietary consumption of the n-3 polyunsaturated fatty acids (PUFA) eicosapetaenoic acid (20: 5n-3; EPA) and docosahexaenoic acid (22: 6n-6; DHA) is associated with their incorporation into circulating phospholipid and increased production of lipid peroxide metabolites. The relationship between peripheral blood mononuclear cell (PBMC) function, n-3 PUFA intake and antioxidant cosupplementation is poorly defined in RHEUMATOID ARTHRITIS (RA) patients. This study was designed to evaluate tumor necrosis factor-a (TNF-a) and interleukin (IL) 6 production by PBMC in RA. Fifty-five patients (50 female, 5 male; mean age= 47±11 years) were investigated in three groups in a randomized double-blind clinical trial. Patients were randomly assigned to one of these three groups: group 1 (G1) was received placebo (MCT oil, 2 g/d plus VITAMIN E placebo), the second group (G2) was received N-3 FATTY ACIDS (1.2 g/d; EPA/DHA plus VITAMIN E placebo), and the third group (G3) was received N-3 FATTY ACIDS (1.2 g/d; EPA/DHA) plus 100 IU/d VITAMIN E. Medication dose was intact during the study. Data were compared between groups using analysis of variance (ANOVA). Fish oil N-3 FATTY ACIDS supplementation of diet decreased production of TNF-a (P= 0.007) by stimulated PBMC in G2 and G3 in relation to G1. Also G3 in relation to G2 and G1 showed significant decrease with respect to malonaldehyde (MDA)(P= 0.005). Consumption of omega-3 fatty acids with VITAMIN E not only decreased production of inflammatory parameters but also decreased lipid per-oxidation in RA patients.