N-3 polyunsaturated fatty acid (PUFA)-rich diets are associated with suppression of cell-mediated immune responses, but the mechanisms are unclear. Specific immune responses are initiated by antigen-presenting cells (APC). We have previously shown in vitro that the n-3 PUFA, eicosapentaenoic acid (EPA), inhibits the expression of HLA-DR, an MHC class II molecule required for normal APC function on human blood monocytes. In contrast, docosahexaenoic acid (DHA) enhanced the expression of this molecule on unstimulated monocytes, but both n-3 PUFA suppressed its expression on interferon-gamma (IFN-gamma)-activated monocytes. In the present study we show that when EPA and DHA were combined at the same ratio as is commonly found in fish oil supplement capsules (3:2) there was no significant effect in vitro on the expression of HLA-DR on unstimulated monocytes, but the expression on IFN-gamma-activated monocytes remained significantly inhibited. In the same in vitro system a significant reduction in the ability of IFN-gamma-activated monocytes to present tetanus toxoid antigen to autologous lymphocytes was observed following culture with the combined n-3 PUFA. These findings support previous animal studies which suggest that n-3 PUFA can inhibit the antigen-presenting function of mononuclear phagocytes.