Objectives : In this study, we investigated the mechanism by which Chelidonium majus (CM) regulates nitric oxide (NO) production. Methods : Using mouse peritoneal macrophages, the mechanism by which CM regulates NO or tumor necrosis $factor-{alpha}(TNF-{alpha})$ production was examined. NO release was measured by the Griess method. $TNF-{alpha}$ production was measured by the ELISA method. The protein extracts were prepared and samples were analyzed for the inducible NOS(iNOS) expression and nuclear factor kappa $B(NF-{kappa}B)$ activation by Western blotting. Results : When CM was used in combination with recombinant $interferon-{gamma}{;}(rIFN-{gamma})$, there was a marked cooperative induction of NO production. CM had an effect on NO production by itself. The expression of the iNOS gene was increased in $rIFN-{gamma}$ plus CM-stimulated peritoneal macrophages and almost completely inhibited by pre-treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of $NF-{kappa}B$. The $NF-{kappa}B$ activation was increased in rIFN-{gamma} plus CM-induced peritoneal macrophages. The increased production of NO from $rIFN-{gamma}$ plus CM-stimulated peritoneal rnacrophages was decreased by the treatment with $N^{G}-monomethyl-{_L}-arginine{;}(N^{G}MMA){;}N^{alpha}-Tosyl-Phe$ chloromethyl ketone (TPCK) , and was almost completely inhibited by pre-treatment with PDTC. Furthermore, treatment with CM alone or rIFN-{gamma} plus CM in peritoneal macrophages caused a significant increase in $TNF-{alpha}$ production. PDTC decreased CM-induced $TNF-{alpha}$ production significantly. After CM treatment in HT-29 or AGS cells, cell viability decreased. Conclusions : These findings demonstrate that CM increases the production of NO and $TNF-{alpha}{;}by{;}rIFN-{gamma}-primed$ macrophages and suggest that NF-B plays a critical role in mediating these effects of CM.