Graft atherosclerosis after heart transplantation is a problem that may limit long-term survival. The objective of this study was to establish whether an association exists between graft atherosclerosis, cellular rejection, HLA compatibility, or antilymphocyte antibodies in recipient serum. Results of cineangiograms from 306 recipients were available. Life table and logistic regression analysis identified only a significant effect of cellular rejection on development of angiogram-evident graft vessel disease. A total of 146 allografts obtained at another transplantation or autopsy were also available. Coronary vessel narrowing was measured by planimetry. Linear regression with coronary narrowing as dependent variable established a positive association with history of cellular rejection. No effect was documented for panel reactive antibody level obtained before or after transplantation. We also did not show an impact of HLA mismatch on this process. The lack of HLA antigen effect prompts us to be cautious about linking graft atherosclerosis directly to the rejection event.