In this study, we examined the effect of genistein on the severity of dermatitis and level of serum IgE in NC/Nga (NC) mice. NC mice housed in conventional conditions develop spontaneous atopic-like dermatitis; however, oral administration of 20 mg/kg genistein suppresses the development of dermatitis. We also investigated the levels of serum IgE in genistein-treated NC mice and found that the levels were the same as those in control NC mice. We further investigated in vitro IFN-gamma and IL-4 production from spleen cells upon stimulation with anti-CD3 and anti-CD28 mAbs. IFN-gamma production level in NC mice that received 20 mg/kg genistein was significantly lower than that in control NC mice. In contrast, the production level of IL-4 in genistein-treated mice was not significantly different from that in control mice but tended to increase in a dose-dependent manner.