Double lung transplantation has been successfully introduced for patients with end-stage pulmonary disease and preserved cardiac function. An advantage of this operation compared with heart-lung transplantation is retention of the recipient's heart. The operative dissection, however, may lead to interruption of sympathetic and parasympathetic pathways to the heart and consequent denervation of the native heart. The cardiac innervation of seven double lung transplant recipients was investigated by the heart rate reponse to carotid sinus massage, the Valsalva maneuver, intravenous injection of atropine, and exercise. Five single lung and two heart-lung transplant recipients were studied for comparison. Of the seven double lung transplant recipients, three had abnormal responses to carotid sinus massage, six to the strain phase of the Valsalva maneuver, and five to the release phase of the Valsalva maneuver. Three of six double lung transplant recipients tested had no response to intravenous injection of atropine, and five of seven patients had an abnormal recovery of heart rate after maximal exercise. No patients had a normal response to all interventions, and three patients had responses compatible with complete cardiac denervation. It is concluded that cardiac denervation may occur after double lung transplantation, most likely caused by surgical interruption of sympathetic and parasympathetic pathways during dissection of the recipient's trachea.