We have analyzed the autopsy material of 11 cardiac allograft recipients, whose grafts became nonfunctional less than 1 year after transplantation. All patients had received routine triple-drug immunosuppression. Two of these patients showed accelerated transplant arteriosclerosis; the graft loss was associated with strong intimal proliferative response affecting the first-order and second-order intramuscular branches of the major coronary vessels. Histologic evidence showed only a slight inflammatory reaction in the vascular adventitia. The media was mostly intact, and the internal elastic lamina showed occasional breaks. A very prominent inflammatory reaction was noted in the subendothelial space in the intima. Immunohistochemistry with monoclonal antibodies revealed that the luminal part of the intima was invaded by anti-leukocyte common antigen and anti-UCHL1 positive T lymphocytes, whereas the abluminal part consisted mostly of anti-smooth muscle alpha-actin-positive smooth muscle cells. We call this subendothelial accumulation of lymphocytes endothelialitis. The suggestion has been made that accelerated arteriosclerosis may be associated with cyclosporine treatment. Correlation with the recipient's cytomegalovirus status in this study suggests that cytomegalovirus infection may contribute to the development of endothelialitis and accelerated arteriosclerosis in heart transplant recipients.