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Not AvailableChronic Respiratory Disease (CRD) is a major problem causing morbidity and mortality which leads to economic loss to the poultry industry. The present research was carried out to study the gross, microscopic and ultrastructural changes in target tissues of natural cases of CRD and to detect the presence of causative pathogenic M. gallisepticum and M. synoviae. Routine post mortem examination of birds submitted to Avian Health Laboratory, DPR, Hyderabad were carried out and from selected CRD cases, the presence of M. gallisepticum and M. synoviae was confirmed by PCR. Results showed a higher prevalence of M. synoviae (25.98%) than M. gallisepticum (9.45%) in samples collected from CRD affected birds. Gross lesions included cloudiness of air sacs, presence of caseous mass in the air sacs, congested tracheal mucosa with catarrhal exudates and caseous materials and congestion and oedema of lungs. Occasionally, sinusitis, conjunctivitis, pericarditis, perihepatitis and salpingitis were also observed. Microscopic changes were edema, congestion and infiltration of mononuclear cells. Ultrastructural studies showed nucleoplasmolysis, margination of nuclear chromatin and swelling of perinuclear cisternae, dilatation of RER and swollen and damaged mitochondria in the air sac and trachea of birds suffering from CRD and positive for M. synoviae.ICA