The data indicated a positive correlation exists between in vitro adherence capability and in vivo pathogenicity of M. hyopneumoniae clones. Results obtained with the in vitro microtiter plate adherence assay indicated that it can be used to estimate the pathogenicity of strains. However, low adherence capability and possibly pathogenicity were not stable as indicated by the shifting adherence capability of M. hyopneumoniae during in vivo growth. In this study, the in vivo environment apparently favored development of a population of more adherent M. hyopneumoniae. Further research to identify immunogenic, protective proteins involved in this phenomenon could enable development of improved M. hyopneumoniae vaccines.