We report here the use of an alternative carrier diphtheria toxoid (DT) in human subjects to overcome antigen-specific unresponsiveness upon immunization with a hapten/ligand-carrier conjugate. In the phase I clinical trial of a birth control vaccine using gonadotrophin subunits linked to tetanus toxoid, some of the subjects failed to evoke a booster antibody response to human chorionic gonadotrophin (hCG). Presentation of the ligand on DT instead in subsequent immunizations restored anti-hCG response.