Since the commencement of the St. Vincent's Transplant Programme, 41 patients have undergone orthotopic heart transplantation, with low-dose cyclosporine and prednisolone as maintenance immunosuppression. An actuarial survival rate of 75% at 1 year resulted. To reduce early rejection-related death, azathioprine was chosen as an augmenting immunosuppressive agent to be administered as a prospective randomized trial. Sixty patients were randomized; 29 received low-dose cyclosporine plus azathioprine plus prednisolone (group A). Thirty-one patients received cyclosporine and azathioprine alone (group B). Both groups received a 7-day course of antithymocyte gamma globulin. One group B patient who underwent retransplantation was not analyzed. Actuarial survival for group A was 92% and group B 93%. The overall incidence of rejection for group A was 1.1 per patient and group B, overall, 2.3 episodes per patient. Group B patients who had persistent rejections were converted to group A protocol. Nine group B patients (30%) required conversion to maintenance steroids (group C). The overall incidence of infection was 1.6 episodes per patient and 1.3 episodes per patient for group A and group B, respectively. Two early deaths in group B and one in group A were unrelated to immunosuppressive protocol. One group A patient died at day 280 of multiorgan failure. There were no rejection- or infection-related deaths in the series. Hypertension occurred with equal frequency in both study groups. The cyclosporine and azathioprine protocol produces actuarial survival and morbidity rates comparable to those of a matched triple-therapy group. Thirty percent of patients in this protocol, however, will require maintenance steroids.