Since 1981, at the University of Minnesota, and more recently at Washington University in St. Louis, cyclosporine has been used as the main immunosuppressive agent for heart transplantation. It was initially combined with prednisone and given in a manner similar to that described at Stanford. In late 1983, concern regarding the nephrotoxic side effects of cyclosporine were heightened due to the fact that a potential recipient had chronic renal insufficiency secondary to renal damage suffered during previous heart surgery. In this patient it was decided to use lower doses of cyclosporine and to add azathioprine to maintain adequate immunosuppression. Initially, the same prednisone therapy was employed. This patient had an uncomplicated course following heart transplantation and was discharged with a normal renal function. This experience was the origin of a trial consisting of using cyclosporine, azathioprine, and prednisone as immunotherapy for heart transplantation. This report describes the results of this therapy in 17 patients.