Cardiac transplantation is now accepted as the therapy of choice for irreversible, advanced heart failure. Improving results have been observed since 1980. This is the consequence of better defined criteria for selection of recipients, refined use of antilymphocyte serum, improved myocardial preservation methods, and the introduction of cyclosporine. Cyclosporine, a metabolite of a soil fungus, is one of the most potent and specific immunosuppressants yet discovered. Its main drawbacks are nephrotoxicity and hepatotoxicity. The immunosuppressive protocol usually includes cyclosporine and low dose steroid. Overall one-year survival has reached 80% to 85%, with a two-year survival of 65% to 75%. The incidence of rejection remains stable despite the use of cyclosporine, but rejection-related morbidity and mortality have been decreasing since 1980. Endomyocardial biopsy of the right ventricle provides good morphologic criteria for assessing the degree of rejection. The absence of myocardial edema during rejection in cyclosporine treated patients appears to be responsible for the limited hemodynamic deterioration and electrographic changes. Morbidity and mortality due to infection have been reduced with cyclosporine, as well. Lymphoma is still common after heart transplantation and may be related to high cyclosporine doses used in the beginning of the clinical trials. Accelerated coronary atherosclerosis of the graft is now the major factor limiting long-term survival and is probably related to chronic rejection. Human heart-lung transplantation began in 1981 at Stanford after excellent clinical results with cardiac transplantation. The success of early attempts was attributed to the use of cyclosporine and the use of combined heart-lung replacement.(ABSTRACT TRUNCATED AT 250 WORDS)