In heart transplantation, accelerated graft arteriosclerosis leading to late postoperative graft failure is still an unsolved problem, and its pathogenesis is poorly understood. The existence of multiple underlying mechanisms has been discussed without conclusive results. In kidney transplantation, a negative influence of cytomegalovirus infection on long-term graft function and patient survival could be demonstrated. To evaluate the role of this infection on the incidence of coronary artery disease in the transplanted heart, we have analyzed the cytomegalovirus serostatus in 38 long-term survivors of orthotopic heart transplantation. In 14 patients (group A) graft arteriosclerosis was diagnosed by means of coronary angiography. In 24 patients (group B) the coronary vessels showed no pathologic findings. In 10 patients (71%) of group A serologic study showed evidence of cytomegalovirus infection, whereas only five patients (24%) of group B revealed cytomegalovirus infection. In two further patients of this group herpes zoster infection occurred (p less than 0.0001). Cytomegalovirus infection seems to be an important factor in the development of accelerated graft arteriosclerosis in the transplanted heart.