Patients with severe sinus-node dysfunction that required pacemaker implantation after orthotopic heart transplantation were reviewed. During a 21-month period, 42 transplantations were performed in 41 patients. Five patients (12.2%) required a permanent pacemaker because of severe dysrhythmias. Three patients had moderate-to-severe cellular and/or humoral (vascular) rejection, and two of the five patients (40%) died. In the remaining two patients, bradyarrhythmias were due most likely to trauma to the sinus node during harvesting of the donor heart, and these patients have shown no evidence of significant rejection on repeated biopsies. A strong relationship was found between moderate or severe rejection and the development of significant bradyarrhythmias that required the placement of a permanent pacemaker. The development of severe dysrhythmias during the early or late posttransplantation period should be considered a manifestation of an ongoing rejection episode until proven otherwise. In our experience this evidence of rejection may imply a poor prognostic sign because it is associated with high mortality rates.