The present study was undertaken to compare the features of monoclonal antibody (mAb) anti-idiotope (Id) induced by complementary peptides, synthesized on the basis of inverted hydropathy for a myelin basic protein (MBP) peptide, or by conventional methodology using Id-bearing antibodies to the same MBP peptide as immunogen. The six reagents studied consisted of mAbs reactive with MBP peptide acetyl 1-9 and MBP peptide 80-89 and anti-Id reagents against these two mAbs prepared by either the complementary peptide or the conventional approach. ELISA, immunoblotting, immunoinhibition of hybridoma cell production of Id-bearing mAb to MBP, and FACS indicated that the anti-Ids generated by either technique were similar although existing in a range reflecting biologic phenomena. mAbs anti-Id prepared by either method continued to show an IgM isotype preference, possibly related to technical considerations, and continued to recognize a cross-reactive Id on the kappa light chain of the mAbs to MBP peptides acetyl 1-9 and 80-89. There was no indication that the anti-Ids prepared by the complementary peptide approach were restrictive or selective in a manner different from those made by the conventional approach.