Monoclonal antibodies (MAbs) specific for surface antigens of lymphocytes are being used to target and deplete tumorous or normal lymphocytes in vivo. Here, we report evidence for the existence of antigenic epitopes on IgE that are accessible on IgE-secreting B cells but not on other cells bearing IgE. Among 42 murine MAbs specific for human IgE, two were shown by fluorescence flow cytometric analyses to bind to IgE-secreting cell lines but not to IgE bound to high-affinity IgE. Fc receptors (Fc∈RI) on basophils or low-affinity IgE receptors (Fc∈RII) on other cell types. Neither could they induce histamine release from basophils of various donors even under very permissive conditions. These antibodies may be useful for targeting IgE-secreting B cells in patients suffering from IgE-mediated allergies.