To evaluate the changes in left ventricular filling associated with acute cardiac rejection, serial Doppler echocardiographic examinations were prospectively performed on the same day as endomyocardial biopsy in 55 consecutive patients who successfully underwent orthotopic transplantation and were free of a previous episode of rejection. On average, 8.6 Doppler studies per patient were performed within a 6 month period after transplantation. Recordings of mitral flow were made with pulsed Doppler and two-dimensional echocardiography from an apical four chamber view; isovolumic relaxation time, peak early mitral flow velocity and pressure half-time were measured. The patients were classified into two groups on the basis of the histopathologic findings: group I (25 patients with at least one episode of mild or moderate rejection) and group II (30 patients without rejection). In group I, rejection was associated with a significant decrease of isovolumic relaxation time (p less than 0.005) and especially pressure half-time (p less than 0.0005) with no change in heart rate and peak early mitral flow velocity. In group II, Doppler indexes remained unchanged. These changes were not associated with alterations in left ventricular systolic function assessed by echocardiography. Isovolumic relaxation time and pressure half-time both returned to values similar to baseline values after immunosuppressive therapy (p less than 0.05 and p less than 0.0005, respectively). With 20% decrease in pressure half-time as a criterion for acute rejection, sensitivity was 88%, specificity 87% and positive predictive value 85%. Thus, Doppler echocardiographic evaluation of left ventricular diastolic function provides an excellent tool for early detection of acute rejection and noninvasive monitoring of the cardiac transplant recipient.