Murine monoclonal antibodies (MAbs) selective for an idiotope on a monoclonal antibody (IgG1/kappa) to human myelin basic protein (MBP) peptide 80-89 were prepared by immunization with a synthetic decapeptide specified by RNA that is complementary to the mRNA for human MBP peptide 80-89. The monoclonal anti-idiotypic antibody (anti-ID) reacted with the MAb to human MBP peptide 80-89 but not with a MAb to bovine MBP peptide 79-88 or to murine myeloma IgG1. The reaction between the monoclonal anti-ID and the MAb to the human MBP peptide 80-89 could be inhibited by human MBP peptide 80-89 and to a more limited degree with human MBP peptide 76-85 and bovine MBP peptide 79-88, but not by human MBP peptides 69-81 and 85-96. Practically, the use of a complementary peptide for stimulating an anti-ID response permits a more selective and feasible method for peparing anti-ID reagents. Theoretically, these results provide further support for the molecular basis of the network hypothesis. © 1989.