The etiology of chronic rejection is most probably multifactorial. The common feature in all organ allografts undergoing chronic rejection is persistent perivascular inflammation and a concentric generalized arteriosclerosis affecting all first and second order intramural arteries. A hypothesis is presented that low-grade damage to endothelium induces the secretion of growth factors which, in turn, are responsible for smooth muscle cell replication and their influx into intima.