Coronary artery morphologic features of 61 human cardiac allografts of short- and long-term survival were correlated with coexisting myocardial pathologic findings and cause of death. On the basis of distribution of coronary lesions, allografts were divided into two broad groups: those with fibrous or atherosclerotic lesions confined to the proximal region of epicardial arteries and those with diffuse necrotizing vasculitis or atherosclerosis of the entire coronary arterial system. Within the two groups, coronary artery morphologic features varied in a time-dependent fashion. Disease in the proximal region began as concentric fibrous intimal thickening, with atheromatous lesions observed after 1 year after transplantation. Five of 10 (50%) patients with atheromatous plaques in the proximal region of arteries died or underwent retransplantation because of coronary disease, as compared to only 1 of 29 (3%) patients with fibrous intimal thickening only in the proximal region. The earliest form of diffuse disease was a necrotizing vasculitis, which was invariably associated with acute myocardial rejection. Long-term survivors with diffuse disease showed severe fibrous or fibrofatty intimal lesions of the large and small epicardial and intramyocardial arteries. In some, diffuse disease may have resulted from healing of necrotizing vasculitis. Eight of nine (89%) long-term survivors with diffuse coronary artery disease died or required retransplantation because of coronary vascular disease. The coronary artery disease of human cardiac allografts is a heterogeneous phenomenon with variable distribution, morphologic features, severity, clinical significance, and, possibly, pathogenesis.