Flavonoids have been reported to demonstrate their benefits in lowering oxidative stress and beneficial effects on cardiovascular and chronic inflammatory diseases. Common phenolic compounds, including phenolic acids, flavonols, isoflavones, and anthocyanins, present in fruits, vegetables, and grains were investigated for their effects on the production of tumor necrosis factor alpha (TNF-alpha) in LPS/IFN-gamma-activated RAW 264.7 macrophages. Gallic acid and (+)-catechin showed small but significant effects, whereas chlorogenic acid had no effect on TNF-alpha production. The flavonol quercetin inhibited TNF-alpha production, but kaempferol and myricetin induced the secretion of TNF-alpha. The isoflavone genistein was an inhibitor of TNF-alpha, whereas daidzein induced TNF-alpha production. Glycosylation of genistein changed its inhibitory effects to TNF-alpha induction, and glycosylation of daidzein had no effect on its activity. Anthocyanidins/anthocyanins and anthocyanin-rich extracts induced TNF-alpha production and acted as modulators of the immune response in activated macrophages. This is the first study to report the effects of anthocyanins and berry extracts on TNF-alpha production.