The production of nitric oxide (NO) and other reactive nitrogen intermediates by cytokine-activated rodent cells is an important component of antimicrobial and/or antineoplastic activity of these cells. This pathway involves the oxidation of arginine to citrulline, with the concomitant release of NO by an inducible form of NO synthase (iNOS). Numerous cell types express iNOS after stimulation with bacterial products and/or cytokines. The role of NO and its derivatives in host resistance is a subject of intense investigation in mouse models of infections or neoplasia. Although human cells such as hepatocytes and endothelial cells have been shown to express an inducible NO synthase, the presence of such a pathway in human monocytes/macrophages has been questioned by many investigators and is a subject of great controversy. In this short review, we discuss some salient points of this debate.