This multidisciplinary project is directed primarily toward evaluation of the therapeutic value of cardiac transplantation for advanced forms of heart disease irremediable by standard forms of therapy. Specific goals include 1) definition of clinical criteria for the selection of cardiac transplant recipients and evaluation of the effects of various physiological and pathological factors present preoperatively on recipient survival and function after transplantation, 2) investigation of tissue typing and immunological responsiveness in the selection of potential cardiac recipients, 3) development and validation of techniques for the diagnosis of acute cardiac allograft rejection in man, 4) the automation of longterm physiological studies (electrocardiographic and ultrasonic) in cardiac recipients, 5) management of psychological and social stresses associated with cardiac transplantation, and 6) evaluation of the late postoperative functional capacity of the transplanted human heart and investigation of late postoperative metabolic and pathological abnormalities associated with biological cardiac replacement.