Radionuclide assessment of ejection fraction was determined early and late postoperatively following cardiac transplantation in 16 patients. In 11 patients, ejection fraction was determined within 48 hours of an endocardial biopsy. There was no relationship between the severity of histologically evident rejection and the ejection fraction (Pearson correlation coefficient [r] = − 0.11; p = 0.47). In 2 patients, severe graft fibrosis developed with consequent diminution in ejection fraction. There was no relationship between severity and duration of rejection or the amount of immunosuppression required to treat acute rejection and the development of graft fibrosis. The mean resting ejection fraction in 7 patients in follow-up ranging from 6 to 21 months after transplantation was 0.59 ± 0.06 (standard deviation), and the mean exercise ejection fraction in 6 of these patients was 0.72 ± 0.08. Radionuclide-determined ejection fraction is not predictive of rejection early after operation. During short-term late follow-up, systolic left ventricular function at rest and exercise has been retained at normal levels.