Background: Monitoring of post-transplant heart rejection is currently based on endomyocardial biopsy analysis. This study aimed to assess the effects of heart graft rejection on myocardial electrical impedance. Methods and results: Twenty-nine cardiac transplant patients and 9 controls underwent measurement of myocardial electrical impedance using a specifically designed amplifying system. The module and phase angle of myocardial impedance were measured. Histopathological rejection grading was performed according to ISHLT classification. Fifty impedance tests were performed in transplanted patients. Myocardial impedance (Z) was higher in controls than in transplanted patients (p < 0.001) and followed a progressive decline at increasing current frequencies (p < 0.001). Likewise, the phase angle of impedance in controls ranged from positive values at low frequencies to negative values at higher frequencies (from 2.5 ± 0.9° at 10 kHz to - 3.8 ± 2.1° at 300 kHz, p < 0.001). Rejection was associated with a significant decrease in myocardial impedance (Z) (15 ± 6.6 Ω in grade 0, 13 ± 6.0 Ω in grade 1A, and 3.3 ± 0.9 Ω in grade 3A at 10 kHz, p < 0.003). Conclusions: Mild degrees of cardiac graft rejection are associated with significant changes in myocardial electrical impedance in transplant patients. Further clinical investigation is warranted to assess the potential of cardiac impedance to detect heart graft rejection. © 2008 European Society of Cardiology.