Recurrent cardiac rejection is a major cause of morbidity during the initial 6 months following transplantation. We compared treatment with tacrolimus versus total lymphoid irradiation in 13 heart transplant recipients on a cyclosporine, azathioprine, and prednisolone regimen, who experienced repetitive rejection. The mean number of episodes of rejection significantly decreased in both groups, with no deaths and no increase in the incidence of infection, hypertension, diabetes, or renal impairment following either treatment at 12-month follow-up. Conversion to tacrolimus or a course of lymphoid irradiation are equipotent strategies, of comparable cost, for the prevention of further rejection in patients with recurrent rejection.