The registration of intramyocardial ECG amplitudes (IMEG) is a non-invasive diagnostic method of monitoring cardiac allograft rejection. Inorder to detect possible sources of error IMEG signals were recorded inheterotopic neck hearts in ten beagle dogs. Immunosuppression was based oncyclosporin A. The rejection process was followed by IMEG registrations aswell as by serial myocardial biopsies. Intramyocardial electrogramrecordings were made via three unipolar and three bipolar leads obtainedfrom screw-in electrodes in both ventricles and the apex of the allograft.A 10% voltage drop was used as an indicator of rejection. In four dogs, thefirst rejection episode was treated with methyl-prednisolone and thetherapy's success was monitored by IMEG and repeat biopsy. At autopsy thehistology of each electrode circumference was correlated with thecorresponding IMEG. The average sensitivity of a single lead was notacceptable (unipolar: 28%, bipolar: 47%). When the voltages of differentleads were summed up the sensitivity rose to 43% (3 x unipolar), 85% (3 xbipolar) and 100% (all leads). During rejection therapy the IMEG recoveredwithin 24-48 h. We conclude that in moderate allograft rejection (grade2/3a ISHT classification), the rejection-related changes of intramyocardialECG voltage amplitude (IMEG) seem to follow a "focal pattern" similar tothe histology. Therefore the recording of several, preferably bipolar,electrode configurations appears to enhance adequate diagnosticreliability.