The risk factors, clinical associations, and response to treatment of cytomegalovirus (CMV) pneumonia and infection were studied in 65 recipients of heart-lung transplantation. There were 29 episodes of CMV pneumonia in 22 patients. In 80% (20/25) of episodes of CMV pneumonia treated with intravenous ganciclovir, the histologic changes resolved and the patient survived. Among seronegative recipients, a seropositive donor was a significant risk factor for CMV pneumonia and infection in the first 90 days after heart-lung transplantation (P = .004 and .002, respectively). Among seropositive recipients, there was no additional risk associated with a seropositive donor. Rates of CMV pneumonia and infection were significantly increased when treatment with augmented immunosuppression had been given in the preceding 30 days (P < .001). A significant association was found between CMV pneumonia or infection and pulmonary bacterial infections occurring 30 days before or after such an episode (P < .001).