This study was undertaken to electrophysiologically find signs of rejection after heart transplantation. A donor heart with a created atrial septal defect was implanted in the retroperitoneal space by anastomosing the thoracic aorta and left pulmonary artery of the donor heart to the abdominal aorta and inferior vena cava of the recipient heart, respectively. Endocardial leads were set up in the right atrium in the vicinity of the bundle of His and in the right ventricle. Cyclosporine (10 to 18 mg/kg/day, continuously) and prednisolone (1.0 mg/kg/day, for the first 4 days) were given orally. Electrophysiologic examinations were performed 1 to 4 days (control data) after the transplantation and were compared with data obtained 5 to 21 days after operation on 12 mongrel dogs. Finally, histopathology of the donor heart was studied. Results showed that the effective refractory period (ERP) of the atrioventricular conduction system was prolonged in six animals from 120 +/- 25 to 192 +/- 35 msec (p less than 0.02) on average. The ERP of the ventricle was shortened in four dogs from 153 +/- 36 to 123 +/- 17 msec (p less than 0.05). Specimens disclosed mononuclear cell infiltration in the atrioventricular node, the bundle of His, and the right and left bundle branches in eight of 12 cases and mild to moderate myocyte damage with cell infiltration in the ventricular septum of the same eight hearts. The ERP of the atrioventricular conduction system showed no change in four cases without mononuclear cell infiltration in the conduction system. These results suggested the feasibility of electrophysiologic monitoring as a means for detecting acute rejection in the prenecrotic stage in transplanted hearts.