Left ventricular diastolic function was evaluated in 41 heart transplant patients during acute rejection by an analysis of echocardiograms and surgically implanted intramyocardial tantalum markers. In 35 patients, isovolumic relaxation time was calculated from M-mode tracings selected from two-dimensional echocardiographic recordings. A total of 84 biopsy findings of no rejection, moderate rejection, and severe acute rejection after treatment were correlated with measurements of isovolumic relaxation time. In six patients, end-diastolic volume, end-systolic volume, stroke volume, ejection fraction, and peak filling rate were obtained from biplanar cineradiographic images of intramyocardial markers. Data from 11 prerejection periods were compared with those of moderate acute rejection. All echocardiograms and marker images were analyzed without previous knowledge of biopsy findings. At times of acute rejection, isovolumic relaxation time decreased from 107 to 65 msec (p less than 0.01) and returned to 98 msec after immunosuppressive therapy. Ejection fraction and end-systolic volume did not change significantly with acute rejection, whereas stroke volume decreased from 76 to 67 ml (p less than 0.05). In contrast to the effects on systolic function, episodes of acute rejection were accompanied by a decrease in end-diastolic volume from 166 to 153 ml (p less than 0.01) and a reduction in peak filling rate from 514 to 460 ml/sec (p less than 0.05). These data suggest that acute cardiac rejection is associated with relative preservation of left ventricular systolic performance but with alterations in diastolic dynamics similar to those seen in "restrictive" cardiomyopathy.