This study is investigating - 1) several methods of immunologic control applicable to cardiac transplantation, 2) a new in vitro, cell-mediated immunity, cytotoxicity assay, and 3) the effect of cardiac denervation on the regional distribution of blood during exercise: 1. In the area of immunological control we are studying the advantages and disadvantages of cyclophosphamide versus azathioprine with antithymocyte globulin in the canine cardiac model. An antiplatelet aggregating agent is being used in long-term grafts to evaluate its effect on the lesions of chronic vascular obliteration. The use of donor-specific antigen with cyclophosphamide is being investigated in an attempt to treat rejection crises and/or to induce tolerance. 2. The possibility of using avian non-complement fixing anti-donor antibody to prevent rejection is being investigated. An in vitro, cell-mediated, cytotoxicity test has already been worked out in the rat system. This study is investigating its use in the dog, and using the test for the diagnosis of rejection and for the detection of blocking antibody. 3. Finally, the regional distribution of blood flow in response to exercise is being examined. The above program provides training for cardiovascular surgery fellows and students in the surgical, physiological and immunological aspects of cardiac transplantation.