Discrepant results have previously been reported concerning long-term left ventricular function in the human transplanted heart as assessed by radionuclide ventriculography. In this study, radionuclide ventriculograms were obtained at rest and during exercise in 19 patients < 6 months, 7-12 months, 13-24 months and > 24 months after transplantation. Ejection fraction decreased significantly from < 6 months to 13-24 months after transplantation (rest: 69.1% +/- 9.7% to 56.7% +/- 8.3%, P < 0.05; exercise: 70.4% +/- 11.3% to 59% +/- 8%, P < 0.05). Heart rate increased significantly during exercise after > 2 years (90.2 +/- 10.5 beats/min to 103.5 +/- 15 beats/min, P < 0.05) but not within 6 months after transplantation (98.5 +/- 12.8 beats/min to 99.07 +/- 15.8 beats/min). Left ventricular end-diastolic volume remained unchanged. Peak filling rate at rest decreased significantly from 4.2 +/- 0.96 edv/s < 6 months after transplantation to 3.3 +/- 0.66 edv/s (P < 0.05) 13-24 months and 3.3 +/- 0.64 edv/s (P < 0.05) > 24 months after cardiac transplantation. Exercise peak filing rate did not change significantly. It is concluded that radionuclide ventriculography demonstrates a decrease in systolic left ventricular function in the long-term course after cardiac transplantation. A significant increase in exercise peak heart rate may be due to autonomic reinnervation. Differences in the literature concerning left ventricular function may be due to different observation intervals following cardiac transplantation.