Anti-idiotypic (Id) antibodies provide a means other than antigen of clone-specific regulation of immune responses, and have been proposed as an alternative form of vaccine. However, the requirements for effective induction of immunity by anti-Id are not understood. Nine monoclonal anti-idiotope antibodies (anti-Id mAb) were derived in the Ia. 7 model system. While all nine anti-Id mAb induced comparable Ab3 responses in vivo as detected by ELISA, there were dramatic differences in the potency of the antigen-specific components of the responses induced by the nine anti-Id mAb. Anti-Id mAb that were indistinguishable in isotype, combining site relatedness, fine specificity on a panel of mAb, end point binding titers, competitive binding and ability to induce Ab3 differed dramatically in their ability to induce antigen-specific immunity in vivo, thus ruling out several models for explaining differences in induction.