The value of pulsed-wave transmitral Doppler for the diagnosis of moderate acute rejection was examined in a total of 347 Doppler recordings obtained in 32 consecutive cardiac allograft recipients. Serial Doppler examinations (median, 11 per patient; range, 1 to 23) were performed simultaneously with endomyocardial biopsies from the first week after heart transplantation to a follow-up of 186 days (median; range, 10 to 395 days after transplantation). Pulsed-wave transmitral Doppler did not allow noninvasive diagnosis of moderate acute rejection in individual patients. Peak filling rate normalized for mitral stroke volume, early diastolic velocity, and mean diastolic velocity were significantly increased, whereas diastolic filling period was decreased during moderate acute rejection compared to other biopsy classes. The wide overlap of measurements in individual recipients with or without rejection may be due, however, to a variety of hemodynamic factors after transplantation affecting diastolic function, which are superimposed on the restrictive left ventricular filling pattern caused by persistent mild acute rejection and left ventricular hypertrophy. These hemodynamic factors include pulmonary hypertension, perioperative ischemia, reperfusion injury, and changes in both blood pressure and loading conditions caused by hypertension and its treatment. Differences between studies with regard to the detection of moderate acute rejection by transmitral Doppler may be caused by chance, because most studies were relatively small. Differences in methods, patient selection, duration of follow-up, prevalence of hypertension and left ventricular hypertrophy, and differences in antihypertensive drug regimens may also play a role. Furthermore differences in the incidence of mild acute rejection, its treatment, and the type of maintenance immunosuppressive regimen used may have influenced the outcome of these studies considerably.