Three hundred thirty-eight endomyocardial biopsies, performed as part of the routine annual evaluation at 1 or more years after transplantation in 211 patients, were reviewed. In only two instances (0.6%) were the histologic findings suggestive, but not pathognomonic, of acute rejection. Both patients were treated for rejection and are doing well at 4 and 6 years postoperatively. On the basis of the results of this study, we believe that routine yearly heart biopsies in asymptomatic patients are not necessary for long-term care of patients after heart transplantation, and we believe they should be performed only if there is clinical suspicion of rejection or as part of a research protocol.