A 50-year-old woman presented with signs of mild heart failure 16 months after orthotopic heart transplantation. Cardiac biopsy revealed ISHLT Grade 2R rejection, which was treated with corticosteroids. Electrocardiograms (ECGs) after transplantation showed a pre-excitation pattern; the presenting ECG showed complete loss of pre-excitation, which returned fully within 7 days of steroid therapy. Intermittent pre-excitation had been present for 4 weeks prior to any other clinical sign of rejection. Accessory pathways can display reversible loss of function during acute cellular rejection, and this may precede other clinical signs. This rare but significant finding may have clinical relevance to other transplanted patients with pre-excitation.