IG12, a syngeneic monoclonal anti-idiotypic antibody, was raised against an idiotype on a monoclonal antibody, ICH2, with specificity for the octapeptide hormone angiotensin II (AII). Competitive radioimmunoassays, and ELISAs utilizing AII antiserum raised in different species (rats and rabbits), indicate that IG12 detects a private idiotypic determinant at or near the paratopic region of the ICH2 combining site. Immunization of syngeneic mice with either IG12 or IG12 coupled to keyhole limpet hemocyanin induced a population of anti-anti-idiotypic antibodies that shared two properties with ICH2: the binding of AII and the binding to IG12. Antibodies from these anti-anti-idiotypic populations were also partially active in inhibiting the interaction between AII and ICH2. To our knowledge, this is the first demonstration of a monoclonal anti-idiotypic antibody mimicking a physiological hormone in inducing a population of anti-hormone antibodies.