Ragweed antigen E loses its major antigenic determinant after denaturation in 8 M urea. The urea-denatured (UD) antigen and α-polypeptide chain isolated from the denatured molecule possess their own antigenic determinant(s) but lack the major determinant of the native molecule. The UD antigen and α-chain, however, are capable of priming mouse T cells specific for antigen E. Priming of A/J mice with the modified antigen enhanced both IgG and IgE antibody responses to antigen E. Both UD antigen-primed spleen cells and α-chain-primed spleen cells collaborate with DNP-primed cells to give an adoptive secondary anti-DNP antibody response to DNP-ragweed antigen in syngeneic irradiated mice. Pretreatment of A/J mice with an i.v. injection of α-chain partially suppressed both IgE and IgG antibody responses to antigen E. Weekly injections of α-chain or UD antigen to antigen E-primed animals depressed on-going IgE antibody response, and suppressed secondary IgE antibody response to antigen E. Transfer of spleen cells from animals treated with the modified antigen to irradiated recipients followed by challenge with native antigen showed that the adoptive secondary response was suppressed by injections of modified antigen to the donors. The results indicate that the immunocompetent cell population was changed by the treatment and provide an experimental model to analyze the immunologic effect of hyposensitization treatment.