To identify electrophysiologic (EP) measurements sensitive to heart transplant rejection, heterotopic thoracic heart transplantation was performed in 11 dogs. Endocardial biopsies were performed daily for up to 9 days, and the severity of rejection was classified as mild, moderate, or severe. Late diastolic thresholds; refractory periods of the left ventricle and right atrium; and conduction times from the right atrium to left atrium, left ventricle to right ventricle, and right atrium to right ventricle were measured daily in transplanted and recipient hearts. The amplitude of the left atrium and right ventricular electrograms was recorded daily. In the recipient hearts no significant EP changes were observed after the second postoperative day. Left ventricular and right atrial refractory periods in both hearts did not change. In the transplanted hearts the conduction times of the right and left atria (but not the conduction time of the left to right ventricles) and right atrium to right ventricle identified moderate rejection; right atrial diastolic threshold was a marker only for severe rejection. Amplitudes of the left atrial and right ventricular electrograms decrease significantly only with severe rejection. At postmortem histologic evidence for rejection was greater in the atria than the ventricles. EP changes in the atria and atrioventricular conduction are more sensitive indicators of acute rejection than ventricular EP changes and correlate with the histologic grade of rejection. None of the measurements evaluated, however, was shown to be a sensitive marker of mild rejection.