In lung or heart-lung transplant recipients, complications as a result of pulmonary infections continue to be the most frequent causes of morbidity and mortality. This study was undertaken to identify the contributions of (1) thoracotomy, (2) interruption of lymphatic vessels and bronchial arteries, (3) transplant procedure, (4) drug-induced immunosuppression, and (5) graft allogenicity to the increased risk of pneumonia in lung transplantation. Lewis rats were inoculated with 10(5) colony-forming units of Legionella pneumophila serogroup 1 by direct instillation into the trachea after one of the following: a general anesthetic with no operation; a left thoracotomy; a left thoracotomy with pulmonary hilar stripping; an isogeneic orthotopic left lung transplant with or without immunosuppression; or an allogeneic transplant with immunosuppression with Brown-Norway rats as donors. Immunosuppression was induced with an intramuscular injection of cyclosporine (25 mg/kg of body weight) from the inoculation day to day 3. All rats were killed on day 6, and severity of infection was determined by quantitative culture of Legionella organisms in the lungs and spleen, titer of Legionella urinary antigen, differential cell count in bronchoalveolar lavage fluid, body weight loss, and gross inspection of the lung. Significant increases in lung Legionella concentration occurred as a result of the addition of pulmonary hilar stripping (from 10(5.13 +/- 0.34) in the thoracotomy group to 10(5.66 +/- 0.25) in the thoracotomy with hilar stripping group, p = 0.013) and the addition of immunosuppression (from 10(5.47 +/- 0.47) in the isogeneic transplant group to 10(6.94 +/- 0.52) in the isogeneic transplant with immunosuppression group, p = 0.00016). Thoracotomy, transplant procedures, and allogenicity itself resulted in no significant increases. The results for all other indicators paralleled those for lung culture. We conclude that the combination of drug-induced immunosuppression with lung denervation and interruption of lymphatic vessels and bronchial arteries results in the early development and increased severity of pneumonia in lung transplantation.