Nitric oxide (NO) formed by the action of inducible form of nitric oxide synthase (iNOS), reacts with oxygen radical forming reactive nitrogen intermediate (RNI). NO and related RNI have been reported to possess antimycobacterial activity. Macrophages can inhibit the proliferation of Mycobacterium tuberculosis by producing NO. In murine models, the ability of macrophages to produce NO can determine the susceptibility of the host to M. tuberculosis and the virulence of M. tuberculosis. However, it is still not clear whether NO is involved in the defense mechanism against M. tuberculosis in humans. We have demonstrated that human peripheral blood mononuclear cells (PBMC) and airway epithelial cells can express iNOS mRNA expression and produce NO production in response to tubercle bacilli stimulation. Furthermore, H37Ra, avirulent strain of M. tuberculosis, induces a larger amount of NO in cultured PBMC than H37Rv, virulent strain, does. There was no difference in NO production between healthy volunteers and patients with tuberculosis. NO production in airway epithelial cells is closely related with IFN gamma concentration. The balance of stimulatory cytokines and inhibitory cytokines for NO production may play a critical role in the defense mechanism against M. tuberculosis considering that NO production is upregulated by IFN gamma, TNF alpha, and IL-1 beta and downregulated by IL-10 and TGF beta. The study of immune response to M. tuberculosis including NO production may give us a better understanding of the pathogenesis of tuberculosis.