Once controversial, the existence of an inducible nitric oxide synthase (iNOS) pathway in human cells is now well recognized. However, the possibility to elicit such a process in human phagocytes and lymphocytes has only been demonstrated recently. Among the stimulus able to trigger the induction of iNOS in human monocytes/macrophages, the ligation of membrane CD23 (FcεRII/ low affinity IgE receptor) gas proven to be one of the most efficient. This CD23-driven NO generation has important consequences, inasmuch as No exerts both physiological regulations, such as the control of release of pro-inflammatory mediators by phagocytic cells, and is also involved in pathological situations, i.e. the onset and progression of some inflammatory and auto-immune diseases. Manipulation of the iNOS pathway through CD23 engagement can be envisaged in order to exacerbate or suppress NO production. Indeed, CD23-driven NO generation is efficient in the destruction of intracellular parasites, such as Leishmania, and modulates the replication of HIV-1 in a model of human monocytic cells. A role for NO in the control of apoptosis has also been reported, notably an anti-apoptotic effect in some populations of human B lymphocytes. We showed recently that tumoral B cells from B cell chronic lymphocytic leukemia and hairy cell leukemia spontaneously display an iNOS activity that can be increased through CD23 ligation and that the NO produced exerts an anti-apoptotic action. Inhibition of this process would therefore favour the reinduction of a normal cell death program and provide a new therapeutical approach in these diseases. In addition, through interaction with its specific receptors on human monocytes, CD11b and Cd11c, which leads to a transient increase in cytoplasmic free calcium concentration, the stable cleavage fragment of CD23, the soluble 25 kDa sCD23, can elicit the activation of another isoform of NO synthase, the constitutive endothelial or type III NOS. This sCD23-driven NO production is involved in the secretion of pro-inflammatory cytokines, such as TNF-α, by these cells. Therefore both the membrane and soluble form of CD23 are endowed with the capacity to trigger the activation of different NOS isoforms in human blood mononuclear cells, which leads to important physiopathological implications.