A chronic respiratory disease of lambs that we have termed the coughing syndrome is characterized by a paroxysmal cough that predisposes to rectal prolapses and secondary bacterial pneumonias. Initial experimentation suggested prevalence and association of mycoplasmas, in particular Mycoplasma ovipneumoniae (MO), with outbreaks of the disease. Experimentation was therefore directed at identifying specific factors or activities of MO that may contribute to the pathogenesis of the disease;A polysaccharide capsule was demonstrated on MO and may contribute to the colonization of ovine respiratory ciliated cells. Expression of the capsule is variable among isolates and is influenced by in vitro culture. Also, strain variation among isolates of the microorganism was associated with the reactivity of the capsule with different lectins. N-acetylglucosamine constitutes the predominant lectin-reactive sugar residue of this capsule;Cytopathic effects were elicited on ovine tracheal ring cultures by MO with loss of ciliary activity and sloughing of epithelial cells. Severity of the effects varied with different isolates of the microorganism and correlated with their ability to produce hydrogen peroxide. Also, the amount of calmodulin released varied between isolates and was directly correlated with ciliostatic activity of the strains of the organism;The experimentation provided evidence for mycoplasma-mediated modulating effects on immune responses of lambs. In lambs infected with mycoplasmas the specific humoral response to MO was delayed and associated with the recovery phase. Autoantibodies to cilia were detected in sera of affected lambs but not in sera from normal lambs. These autoantibodies were predominantly of the IgG isotype and were not cross-reactive with antigens of common bacterial pathogens of the sheep respiratory tract. Also, preliminary evidence suggests that an immediate hypersensitivity is induced to the MO organisms. The ability of MO to upregulate the expression of MHC molecules on sheep alveolar macrophages was demonstrated. This may enable the macrophages to present self antigens to autoreactive T cells during their attempt to eliminate the damaged host cells produced during the ciliostasis event;The findings of the experimentation suggest that aberrant immune responses play a major role in the pathogenesis of the disease.