Background. Complement activation has recently been implicated as a contributing factor to early and late allograft dysfunction in cardiac transplantation. The current study was designed to determine whether measurement of plasma complement fragments C4d and SC5b-9 would be useful in detecting acute rejection or accelerated graft atherosclerosis (AGA) in cardiac allograft recipients. Methods. We measured complement activation products, C4d (classical pathway) and SC5b-9 (terminal pathway), at the time of routine endomyocardial biopsy in heart transplant recipients. Ten patients in the immediate posttransplantation period (0-100 days) and 19 patients more than 6 months after transplantation were studied. Results. No correlation was found between plasma levels of complement activation fragments and the presence of biopsy-proven acute allograft rejection or AGA (assessed by coronary angiography). However, plasma C4d and SC5b-9 were significantly elevated in 9 of 10 and 7 of 10 patients, respectively, in the immediate posttransplantation period. This was followed by progressive decrease in the levels of C4d and SC5b-9 fragments during the first 4-6 weeks after transplantation. Conclusion. We conclude that measuring plasma levels of fragments C4d and SC5b-9 is not a useful noninvasive method for detecting acute rejection or AGA after heart transplantation. However, this study provides further evidence that early complement activation after heart transplantation may play a pathogenic role in allograft injury.