Summary: The skin-sensitizing activity in the sera of nine atopic patients, who are sensitive to ragweed pollen, and in a reagin-rich fraction of another patient's serum was precipitated by anti-γE-globulin antiserum which did not contain any detectable antibody against γG-, γA-, γM- or γD-globulins. Absorption of the skin-sensitizing antibody was accompanied by the loss of γE antibody in the supernatants. The skin-sensitizing activity in the patients' sera, determined by P-K reactions with antigen E, paralleled radioactivity of the γE band which was observed by radioimmunodiffusion with the radioactively-labeled antigen, whereas no correlation was observed between the skin-sensitizing activity and either γG or γA antibodies. When one of the patients' sera was fractionated by chromatography on a DEAE cellulose column, gel filtration, sucrose density gradient ultracentrifugation and by zone electrophoresis on agarose gel, distributions of reaginic activity paralleled those of γE antibody. These findings strongly support the hypothesis that reaginic antibodies in ragweed sensitive patients' sera are associated with γE-globulin. Light chains of immunoglobulins were detected in γE-globulin, indicating that γE-globulin is a new immunoglobulin.