Anti-IgE mAbs have always been used to trigger mediator release from basophils or mast cells. Now nonanaphylactogenic anti-human IgE Abs are in clinical evaluation as a therapeutic agent against atopic disease. We have found a mAb that is nonanaphylactogenic but recognizes receptor-bound IgE. Interestingly, the Ab prevents the association of IgE with its receptor if immune complexes were formed between IgE and anti-IgE mAb. This explained the phenomenon that addition of anti-IgE Ab to receptor-bound IgE resulted in a decrease of receptor-bound IgE, because IgE dissociating from the receptor was complexed, altering the thermodynamic balance of receptor-bound vs free IgE. Our data show that there are nonanaphylactogenic Abs that do not directly interfere with the receptor binding site on IgE and are capable of preventing the association of IgE with its high affinity receptor. This unique feature would render such an anti-IgE Ab a possible candidate for immunotherapy of atopy.