It is established that extremely low frequency magnetic fields (ELFMF) at the flux densities, i.e., 5 mT and less, are not mutagenic. However, exposure to ELFMF enhances mutations induced by X-rays. In this study, we examined the effects of long-term exposure to 5 mT ELFMF on mutation induction and X-ray-induced mutations in human malignant glioma cells (MO54) with different mutant I kappa B-alpha (a critical inhibitor of NF-kappa B) genes. Cells were exposed or sham-exposed to 5 mT ELFMF for up to 8 days with or without initial X-rays (4 Gy), and the mutant frequency of hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene was analyzed. An obvious increase in X-ray-induced mutations was observed after treatment with ELFMF in combination with X-irradiation in MO54 cells with tyrosine mutant I kappa B-alpha gene other than with serine mutant I kappa B-alpha gene or vector alone. Exposure to ELFMF alone increased mutations significantly in MO54 cells with tyrosine mutant I kappa B-alpha gene, In addition, X-ray-induced apoptoic cells were increased in MO54-V cells after exposure to ELFMF, while an anti-apoptotic effect of magnetic field was found in MO54-SY4 cells. Our data suggest that exposure to 5 mT ELFMF may induce mutations and enhance X-ray-induced mutations, resulting from the inactivation of NF-kappa B through the inhibition of tyrosine phosphorylation.