Measuring intramyocardial ECG amplitude is a clinical non-invasive procedure used for diagnosing rejection after heart transplantation. In recent years, as the importance of humoral mediated rejection has increasingly been recognized, the fact that endomyocardial biopsies often produce false negative results due to the absence of lymphocytic infiltrates has become a matter of concern. In order to test the reliability of IMEG diagnosis of this form of rejection, heterotopic neck-heart transplantation was performed on eight beagles which were previously sensitized through several skin transplantations. Over the course of the study IMEG registrations were performed daily as well as echocardiographic examinations to determine left ventricular wall thickness and maximal diastolic relaxation velocity. Donor-specific antibodies in serum (IgG, IgM) were also determined daily. Myocardial biopsies, performed once every 2 days, were examined for the presence of edema and lymphocytic infiltrate (according to the guidelines of the International Society of Heart and Lung Transplantation, ISHLT) and examined under immunofluorescent microscopy of IgG and IgM. Under triple drug immunosuppression with cyclosporine A, azathioprine, and cortisone accelerated rejection occurred on the fifth postoperative day (range: 4th-5th). All eight episodes were detected through IMEG diagnosis (sensitivity 100%), while the myocardial biopsies graded according to ISHLT guidelines indicated only one case of relevant lymphocytic infiltrate (Grade 3A) (sensitivity 12.5%). In each case rejection was recognized so early that it was possible to perform therapy with restitutio ad integrum. This proved that, as opposed to endomyocardial biopsy, IMEG diagnosis detected humoral mediated rejection early and with high reliability. Furthermore, the immediate recovery in IMEG during therapy indicates that the voltage decrease cause by rejection cannot be explained by an irreversible loss of myocardium (myocytolysis), but rather may be due to a quickly reversible functional impairment.