At present the monitoring of heart transplant patients for rejection is done by endomyocardial biopsy. It has been proposed that ECG assessments of conduction delay may provide a noninvasive means of detecting rejection. To determine whether rejection in the atrioventricular node and conduction bundles reflects rejection in the working myocardium, we studied 21 transplanted hearts from 21 cardiac allograft recipients. Twenty of the hearts were obtained at autopsy, and one was obtained from a patient who underwent a second transplant procedure. The atrioventricular conduction tissues, the ventricular and atrial free walls, and the interventricular and interatrial septa from these hearts were examined for histologic evidence of rejection. Of the 21 hearts, 17 showed histologic changes of acute allograft rejection. Of the 17, rejection involved the conducting system and the myocardium equally in 11. In 6 of the 17 hearts, rejection involved the working myocardium more severely than it did the conducting system. Of interest, nonrejection pathologic changes were also noted in the conducting systems of several hearts. Severe accelerated arteriosclerosis was found in the artery to the atrioventricular node in one case, and lesser degrees of accelerated arteriosclerosis in this artery were found in two additional cases. In one case, lymphoid infiltrates, consistent with posttransplant lymphoproliferative disorder, were noted in the vicinity of the atrioventricular node, and several hearts demonstrated operative trauma or ischemic changes that appeared to involve the conducting system. These results suggest that although there may be a morphologic basis for using electrophysiologic changes in the conducting system to monitor heart allograft recipients for rejection, caution should be exercised in interpreting these changes.