The effects of some selected flavonoids on tumor necrosis factor-alpha (TNF)-induced cytotoxicity in murine fibroblast L-929 cells were studied. All of the flavanones tested as well as a flavan, epicatechin, protected L-929 cells from TNF-induced cell death of the flavanones tested, hesperetin, isosakuranetin, and pinocembrin failed to modify TNF cytotoxicity, but the 3',4'-dihydroxyflavanones, eriodictyol and taxifolin, showed a protective effect. Eriodictyol was the most potent protective agent of all the flavonoids tested, while a 4'-hydroxyflavanone, naringenin, rather showed enhancement of TNF cytotoxicity. Of the flavones tested, chrysin and apigenin markedly augmented the cytotoxicity of TNF, while luteolin showed a weak protective effect. The magnitude of protection and potentiation by these flavonoids were concentration-dependent and these effects were not altered when the flavonoids were added as much as 2 h after TNF treatment.