The omega-6 arachidonic acid supplementation of the human promonocytic cell line U937 strongly stimulates the nuclear translocation of the transcription factor NF-kB. Inhibitors of arachidonate oxidative metabolism prevent NF-kB activation, indirectly indicating a role for prostaglandin and leukotriene metabolites in the genesis of this phenomenon. Of note, omega-3 eicosapentaenoic acid does not exert any effect on NF-kB DNA binding. In subsequent experiments, prostaglandin E2 consistently showed the ability to activate NF-kB in U937 promonocytic cells, as well as in J774 macrophages. NF-kB activation by arachidonate, together with the lack of effect by eicosapentaenoic acid, suggests a way to modulate the expression of certain genes by means of a suitable dietary n-6/n-3 fatty acid ratio.