Eosinophils display various receptors for immunoglobulin E (IgE) including the high affinity receptor for IgE (Fc epsilon RI), CD23 (Fc epsilon RII), and Mac-2/epsilon BP. We attempted here to clarify the role of these receptors in IgE-mediated activation of eosinophils from normal human bone marrow cultures. Pretreatment of eosinophils with IL-4 is required for IgE/anti-IgE-mediated stimulation of TNF-alpha and peroxydes production. TNF-alpha release from eosinophils was also induced following ligation of CD23 and to a lesser extent with anti-Mac-2, while Fc epsilon RI-ligation had no effect. IgE/anti-IgE effect dramatically decreased when eosinophils were pretreated with Fab fragments of CD23-mAb. In addition, this effect could also be reversed by inhibiting CD23-dependent nitric oxide pathway by NG-monomethyl-L-arginine. Nitric oxide chemical donor, SIN-1, induced TNF-alpha release from eosinophils. CD23 and nitric oxide pathway are thus involved in IgE-mediated stimulation of normodense human eosinophils.