Abnormally high myocardial performance index (MPI) is a Doppler-derived marker of combined systolic and diastolic left ventricular (LV) dysfunction. To identify early stage allograft dysfunction by MPI, we studied 154 long-term heart transplantation (HT) recipients (131 male, aged 51 +/- 13 years at HT, mean follow up 8.4 +/- 3.5 years), with normal left ventricular ejection fraction (LVEF) and free from acute rejection (AR), and 25 normals (13 male, aged 39 +/- 16 years). Rejection score (RS) on endomyocardial biopsy was calculated in the first year. MPI was prolonged (0.45 +/- 0.18 vs. 0.28 +/- 0.10, P = 0.0001) in patients and directly related with mean time from HT (P = 0.001), higher cumulative dosages of cyclosporine at 3 months (P = 0.01), 6 months (P = 0.03), 1 year (P = 0.02), 3 years (P = 0.04) and with cumulative dosage of methylprednisolone at 1 year (P = 0.002). The index was inversely related with mean age at HT (P = 0.002) and tended to be directly related with RS at 1 year (P = 0.05). Thus, MPI is abnormal in long-term HT recipients with normal LVEF. Its direct relation with time from HT as well as immunosuppressive load suggests an early stage of graft dysfunction because of chronic rejection. Extended prospective studies are warranted to clarify its potential role as a negative prognostic marker in HT.