The effects of secondary forces on monoclonal IgM anti-fluorescein antibody 18-2-3 reactivity were investigated and the results correlated with similar studies characterizing anti-fluorescein mAbs 4-4-20 and 9-40. mAb 18-2-3 was considered an important model for further elucidation of secondary forces since it possessed ligand binding properties similar to mAb 4-4-20, such as a similar affinity, but due to a very different primary structure it was idiotypically and metatypically distinct. mAb 18-2-3 also possessed cryoglobulin (anti-Ig) and extensive cross-reactive properties (e.g. anti-phenyloxazolone) suggestive of an atypical anti-fluorescein active site. The reactivity of mAb 18-2-3 with model fluorescein-peptides was modulated by secondary forces in a manner that differed from both mAbs 4-4-20 and 9-40. Thus, the effects of secondary forces seemed to vary with each monoclonal antibody even though each of the immunoglobulins studied were specific for the same homologous ligand. Results indicated that secondary forces impacted immune complex stability, variable domain conformation and protein dynamics. Models were postulated to account for secondary effects on the mAb 18-2-3 active site relative to mAbs 4-4-20 and 9-40. Levels of hydration, active site architecture and local amino acid dynamics were among the models cited.