A method of hetero-orthotopic heart-lung transplantation is described in the dog. The model was developed to study patterns of rejection in the transplanted heart and lung, since the dog will not survive bilateral pneumonectomy and loss of the Hering-Breuer reflex. After removal of the recipient's left lung the donor heart and left lung are explanted en bloc. End-to-end connection is made of both left main bronchi, and the donor aorta is joined end-to-side with the recipient's descending aorta. An atrio-atrial anastomosis is performed between the recipient's left and the donor's right atrium. Four experiments were done to develop the surgical technique and 10 long-term studies were performed to investigate rejection patterns. The average survival rate of these animals was 28.5 +/- 8.3 days, ranging from 5 to 53 days. Causes of death were not due to operative complications. Heterotopic heart-lung transplantation is an uncomplicated surgical method which does not require cardiopulmonary bypass or anticoagulation and allows the investigator to study heart and lung grafts in dogs for long-term periods after surgery. Bronchoscopy, bronchoalveolar lavage, and heart and lung biopsies of both donor and recipient organs can be performed.