Elevated IgE levels are commonly observed during the inflammatory responses in allergy and a variety of infections. This Ig activates the release of multiple mediators from monocytes/macrophages. In the present work, we attempted to clarify the IgE-dependent events involved in the activation of monocyte functions. IgE-anti-IgE immune complexes induce the production of tumor necrosis factor-alpha, oxygen radicals, IL-6 and thromboxane B2 from normal human purified monocytes. Expression and cross-linkage of Fc epsilon RII/CD23 were essential for these IgE-mediated effects. Cytokine production following CD23 ligation depended on nitric oxide transduction pathway, as it was inhibited by NG-monomethyl-L-arginine, a competitive inhibitor of the conversion of L-arginine to L-citroline by nitric oxide synthase. Furthermore, addition of the nitric oxide chemical donator, Sin-1, enhanced IgE-induced monokine release. CD23-ligation also induced the production of nitrites by these cells. This work linked CD23 to the L-arginine-dependent transduction pathway and shows their involvement in IgE-mediated stimulation of human monocytes.