The membrane IgE peptide (MEP) encompassing 20 amino acids proximal to the C terminus of membrane IgE molecules, and secretory IgE peptides (SEP), spanning CH epsilon 1 to 4 domain were synthesized according to IgE genomic and cDNA sequences. Inhibition of anti-KLH and anti-BGG IgE, but not IgG responses was observed in mice treated with MEP-protein but not SEP-protein conjugates in complete/incomplete Freund's adjuvant. Only IgE responses directed toward proteins to which MEP was conjugated, were inhibited, while IgE responses to a concomitantly injected, unrelated antigen were not. Inhibition of antigen-specific IgE was also not correlated with levels of anti-MEP or anti-IgE antibodies, moreover, levels of total IgE remained comparable among mice treated with MEP-protein conjugates, native or glutaraldehyde-modified protein carriers. This observation may have significant import on future design of IgE immunotherapy. Treatment of MEP conjugated allergens prevents formation of IgE-anti-IgE complexes because the MEP sequence is absent from the secretory IgE.