Basophils and mast cells have the high affinity IgE receptors (FcεRI) on their plasma membrane and play important roles for IgE antibody-FcεRI associated allergic diseases, such as pollen hypersensitivity, food allergy, urticaria and asthma. To date, several reports revealed that high concentration of IgE antibodies activate mast cells in the absence of any antigens. However, IgE antibodies-induced activation of basophils has not been reported. In this study, we investigated if IgE antibodies may regulate functions of human peripheral basophils by itself without antigen in vitro. We first stripped IgE antibodies which were originally bound to FcεRI on human peripheral basophils by treatment with lactic acid. We then demonstrated that high concentration of IgE antibodies (> 1μg/ml) induced histamine release, morphological change, cytokine release and CD203c up-regulation of IgE antibodies-stripped basophils. Thus, high concentration of IgE antibodies directly induce the activation of basophils which express IgE-free FcεRI on their surface. The mechanism may account for antigen-independent pathogenesis of allergic disorders in which serum concentration of IgE antibodies is higher than 1μg/ml.