OBJECTIVE Heart transplant recipients undergo a number of invasive endomyocardial biopsies to screen for rejection. Serum assays of troponin T and/or I may provide a less invasive alternative. The purpose of this study was to evaluate troponin T and I as markers of cardiac transplant rejection. METHODS We conducted a prospective analysis comparing troponin T and I levels to biopsy results in heart transplant recipients. Plasma was assayed for troponin T and I preoperatively, on the first 3 postoperative days, and with each subsequent biopsy. RESULTS Twenty-nine patients entered the study. A total of 173 biopsies were performed at a mean follow-up of 129+/-9 days (range: 12-564 days). There were two rejection episodes (> or = grade 3), one in each of two patients. There were no significant relationships between troponin T or I and biopsy-proven rejection (> or = grade 3; P=0.59 and 0.54, respectively). There were also no correlations between troponin T or I levels and biopsy grade (P=0.40 and 0.92, respectively). Troponin T and I levels peaked on postoperative day 1 and fell to baseline over long-term follow-up with no peak in serum markers associated with rejection episodes. Donor ischemic time was significantly correlated to troponin T on postoperative days 1-3 (r=0.58, P=0.005; r=0.61, P=0.004; and r=0.61, P=0.003, respectively). CONCLUSIONS Troponin T and I are not useful indicators of cardiac rejection, but do correlate with donor heart ischemic injury.