Long-term success of cardiac transplantation is mainly limited by the development of transplant coronary artery disease (CAD); it is generally accepted that it is immune mediated, involving cytokines and growth factors. We show that development of transplant CAD is associated with a particular cytokine profile in myocardial biopsies characterized by a late (i.e., 1 year) increase in tumor necrosis factor-alpha and interferon-gamma gene expression, which precede and potentially contribute to the development of allograft vasculopathy, further supporting a role for inflammation and the pathogenesis of transplant CAD in humans.